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OpenTrials
Completed

NCT Number: NCT02424799

Study to Investigate Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of GSK2646264

This First Time in Human (FTIH) study, which will be performed in three parts, is designed to investigate the safety, local tolerability, pharmacokinetics and pharmacodynamics after single and repeat topical applications of up to 2 strengths of GSK2646264 and corresponding placebo within the same subject, in healthy adult subjects (Part A), subjects with cold urticaria (CU, Part B) and subjects with chronic spontaneous urticaria (CsU, Part C). The study will also measure short term effects of GSK2646264 on the number and size of weals in subjects with CsU, and in healthy subjects and subjects with CU following provocation tests.

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Key information

Conditions

Urticaria Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Skin Diseases Skin Diseases, Vascular Skin and Connective Tissue Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site, Berlin, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for all subjects in Parts A, B and C

  • Male or female subject aged at least 18 years (Yrs) at the time of signing the informed consent. The upper age limit of subjects is defined in the specific inclusion criteria for each cohort.
  • All subjects must be free from scarring or skin markings (e.g. tattoos or piercings) and open wounds (e.g. scarring or skin markings) on the defined areas of the body that cream will be applied onto, unless in the opinion of the investigator it will not compromise the subjects safety and quality of data.
  • Able to refrain from exposure to extended and direct sunlight during the study period, from screening (SCR) until follow up, especially the area that is under treatment during the study.
  • Able to refrain from shaving and waxing the areas on which the study cream will be applied during the duration of the study from SCR to follow up.
  • Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until the follow up visit or a time period that is 5 terminal half-live post-last dose which will be determined following Part A of the study.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Willing, committed and able to return for all clinic visits and complete all study-related procedures. Able to read, understand and complete study- related questionnaires.

Inclusion criteria

specific for healthy subjects (Part A)

  • The subject is aged between 18 and 55 yrs of age inclusive, at the time of signing the informed consent.
  • Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 19 to 30 kg per square meter (m^2 )(inclusive).
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator, in consultation with the GSK Medical Monitor (MM) if required, agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Demonstration of a positive weal and flare reaction (>=3 millimeter (mm) in diameter relative to negative control) to at least one allergen from a battery of allergens (mixed grass pollen, Dermatophagoides pteronyssinus, birch pollen and cat dander) on skin prick testing at SCR.
  • Subjects must be free from any past or present benign or malignant skin conditions and disease, unless in the opinion of the investigator it will not compromise the subject's safety and quality of data.
  • Non-smokers or if the subject is a tobacco smoke: smokes less than 5 cigarettes per day and commits to not smoke tobacco for the duration of the in-house stay, and commits to stable and moderate use (as determined by the Investigator) of tobacco or nicotine-containing products, including nicotine patches/gum, during the course of the study, as long as the patches do not interfere with the study procedures.
  • A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records; or postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milli international unit [MlU]/milliliter [mL] and estradiol <40 picogram (pg)/mL (<147 picomoles/litre) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods described if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.

Additional Inclusion criteria specific for subjects with CU (Part B)

  • Diagnosed with CU for more than six weeks as confirmed by medical history and with a positive cold stimulation test assessed by TEMPTest 4.0 prior to first dose.
  • The subject is aged between 18 and 70 yrs of age inclusive, at the time of signing the informed consent.
  • Body weight >=50 kg and BMI within the range 19 to 35 kg/m^2 (inclusive).
  • Other than a diagnosis of CU, the subject should have no other co-morbidities which would introduce additional risk factors and will not interfere with the study procedures, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator, in consultation with the GSK MM if required, agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedure.
  • In addition, the following criterion will apply to a minimum of 4 patients in Part B: Demonstration of a positive weal and flare reaction (>=3 mm relative to negative control) to at least one allergen from a battery of allergens (mixed grass pollen, Dermatophagoides pteronyssinus, birch pollen and cat dander) on skin prick testing at SCR,
  • Subjects must be free from any past or present benign or malignant skin conditions and disease, other than the specified condition required for eligibility of subjects as defined in the specific inclusion criteria for CU cohort unless in the opinion of the investigator it will not compromise the subjects safety and quality of data.
  • Non-smokers or if the subject is a tobacco smoker: smokes less than 5 cigarettes per day and commits to not smoke tobacco for the duration of the in-house stay, and commits to stable and moderate use (as determined by the Investigator) of tobacco or nicotine-containing products, including nicotine patches/gum, during the course of the study, as long as the patches do not interfere with the study procedures.
  • Female subjects must agree to use one of the contraception methods listed in protocol, 28 days before their SCR visit and until the followup visit or a time period that is 5 terminal half-live post-last dose which will be determined following Part A of the study.

Additional Inclusion criteria specific for subjects with CsU (Part C)

  • The subject is aged between 18 and 70 yrs of age inclusive, at the time of signing the informed consent.
  • Body weight >=50 kg and BMI within the range 19 to 35 kg/m2 (inclusive)
  • Subjects who have a score of >14 on the UAS7 questionnaire with between 4-10 weals observed in a defined area of the body will be included in this study. This area must include either both arms, or both legs or both sides of their torso for 7 consecutive days during the SCR period, prior to the Day 1 visit. If a subject has not completed 7 consecutive days of UAS questionnaire prior to dosing on Day 1 due to exceptional circumstances, the SCR period may be extended until the subject has completed 7 consecutive days of UAS questionnaire. This will only be at the discretion of the Investigator.
  • No other aetiology identified for chronic urticaria such as drug-related or inducible urticaria as determined by history, physical examination and laboratory studies.
  • Subjects must be free from any past or present benign or malignant skin conditions and disease, other than the specified condition required for eligibility of subjects as defined in the specific inclusion criteria for CsU cohort unless in the opinion of the investigator it will not compromise the subjects safety and quality of data.
  • Other than a diagnosis of CsU the subject should have no other co-morbidities which would introduce additional risk factors and will not interfere with the study procedures, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator, in consultation with the GSK MM if required, agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Female subjects must agree to use one of the contraception methods 28 days before their SCR visit listed in protocol and until the follow-up visit or a time period that is 5 terminal half-live post-last dose which will be determined following Part A of the study.

All Cohorts Exclusion Criteria

  • Thyroid stimulating hormone levels outside normal range.
  • Subjects with a history of Graves disease.
  • Subjects with a history of any thyroid cancer.
  • Unable or unwilling to avoid use of topical creams/lotions at sites where medication will be applied. Washing with soap and water will be permitted.
  • Based on averaged corrected QT interval for heart rate (Fridericia's) [QTcF] values of triplicate ECGs obtained over a brief recording period: QTcF > 450 msec; or QTcF >480 milliseconds (msec) in subjects with Bundle Branch Block.
  • Alanine aminotransferase, alkaline phosphatase and bilirubin ≥ 1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or previous history of uncomplicated cholecystectomy.
  • History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • History of sensitivity to any of the study medications, or components thereof, history of anaphylaxis or a history of drug or other allergy that, in the opinion of the investigator or GSK MM, contraindicates their participation.
  • Unable to refrain from vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half lives (whichever is longer) prior to the SCR visit until the completion of the follow-up assessments, unless in the opinion of the Investigator, in consultation with the GSK MM if required, the medication will not interfere with the study procedures or compromise subject safety.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of SCR.
  • A positive test for HIV antibody.
  • Lactating females.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day
  • Use of topical steroids or calcinurin inhibitors are prohibited during the study from SCR to follow up.
  • Exclusion related to prior drug treatments: Intake of oral corticosteroids within 7 days >10 milligram (mg) per day prior to first SCR visit; Use of depot corticosteroids within 7 days prior to first SCR visit; Subjects who are taking anticoagulants (e.g. warfarin) must not be on warfarin within 21 days prior to SCR. Subjects who are having psoralen combined with ultraviolet A (PUVA) treatment must not be using PUVA treatment within 21 days prior to SCR.
  • Subjects who work for the Sponsor, CRO, or one of the study centres. Country Specific Exclusion criteria for Germany that applies to Part A, Part B and Part C.
  • Subjects who live in detention on court order or on regulatory action, see §40 subsection 1 sentence 3 no. 4 AMG. (Arzneimittelgesetz).

Additional Exclusion for Part A - Healthy Subjects

  • Use of H1 antihistamines within 3 days prior to first SCR visit Additional Exclusion for Part B - CU Subjects
  • Exclusion related to prior drug treatments: Use of Zaditen (Ketotifen) within 14 days prior to first SCR visit; Use of Doxepin AZU and other tricyclic antidepressants with antihistaminergic properties within 14 days prior to first SCR visit; Use of H2 antihistamines within 7 days prior to first SCR visit; Use of H1 antihistamines within 7 days prior to first SCR visit; Use of monteleukast or any other leukotriene antagonist within 7 days prior to first SCR visit; Use of biologicals including omalizumab within 5 months prior to first SCR visit.

Additional Exclusion for Part C- CsUpatients

  • Exclusion related to prior drug treatments: Intake of cyclosporin within 10 days prior to first SCR visit; Intake of other immunosuppressant drugs within 28 days of first SCR visit; Use of monteleukast or any other leukotriene antagonist within 7 days prior to first SCR visit; Use of Dapsone within 7 days prior to first SCR visit; Use of Zaditen (Ketotifen) within 14 days prior to first SCR visit; Use of Doxepin AZU and other tricyclic antidepressants with antihistaminergic properties within 14 days prior to first SCR visit; Use of H2 antihistamines within 7 days prior first SCR visit; Use of biologicals including omalizumab within 5 months prior to first SCR visit; Use of H1 antihistamines above the licensed dose within 3 days prior to first SCR visit.

Treatment and study plan

GSK2646264 0.5% topical cream

Drug

GSK2646264 0.5% topical cream is supplied as white-to-off-white aqueous cream stored in amber glass jars

GSK2646264 1% topical cream

Drug

GSK2646264 1% topical cream is supplied as white-to-off-white aqueous cream stored in amber glass jars

Placebo

Drug

Placebo topical cream is supplied as white-to-off-white aqueous cream stored in amber glass jars

Primary outcomes

  1. Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Part A

    Time frame: Up to Day 7

    AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Safety population comprised of all participants who took at least one dose of study treatment.

  2. Number of Participants With AEs and SAEs Part A

    Time frame: Up to Day 11

    AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.

  3. Number of Participants With AEs and SAEs Part B

    Time frame: Up to Day 19

    AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Data is presented according to the percentage BSA as it impacted safety

  4. Number of Participants With AEs and SAEs Part C

    Time frame: Up to Day 23

    AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.

  5. Number of Participants With AEs and SAEs Defined by Severity Part A

    Time frame: Up to Day 7

    AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities.

  6. Number of Participants With AEs and SAEs Defined by Severity Part A

    Time frame: Up to Day 11

    AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities.

  7. Number of Participants With AEs and SAEs Defined by Severity Part B

    Time frame: Up to 19 days

    AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities. Data is presented according to the percentage BSA as it impacted safety

  8. Number of Participants With AEs and SAEs Defined by Severity Part C

    Time frame: Up to 23 days

    AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities.

  9. Change From Baseline in Vital Sign Parameter Heart Rate for Part A

    Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 and follow-up (Day 5 to Day 7)

    Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2, Day 3, Day 4 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

  10. Change From Baseline in Vital Sign Parameter Heart Rate for Part A

    Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up (Day 9 to Day 11)

    Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

  11. Change From Baseline in Vital Sign Parameter Heart Rate for Part B

    Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to Day 19)

    Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

  12. Change From Baseline in Vital Sign Parameter Heart Rate for Part C

    Time frame: Baseline and (Day 1 pre-dose), Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15, follow-up (Day 23)

    Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

  13. Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A

    Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 and follow-up (Day 5 to Day 7)

    Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2, Day 3, Day 4 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

  14. Change From Baseline in Vital Sign Parameters SBP and DBP for Part A

    Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up (Day 9 to Day 11)

    Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

  15. Change From Baseline in Vital Sign Parameters SBP and DBP for Part B

    Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to Day 19)

    Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

  16. Change From Baseline in Vital Sign SBP and DBP for Part C

    Time frame: Baseline (Day 1 pre-dose) and Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up (Day 23)

    Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

  17. Change From Baseline in Electrocardiogram (ECG) Parameters for Part A

    Time frame: Baseline (Day -1) and Day 4, and follow-up (Day 5 to Day 7)

    Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, corrected QT (QTc-Bazett [QTcB], QTC interval-Fredericia [QTcF]) intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

  18. Change From Baseline in Electrocardiogram (ECG) Parameters for Part A

    Time frame: Baseline (Day -1) and Day 8 and follow-up (Day 9 to Day 11)

    Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, corrected QT (QTc-Bazett [QTcB], QTC interval-Fredericia[QTcF]) intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

  19. Change From Baseline in ECG Parameters for Part B

    Time frame: Baseline (Day -1) and Day 3 (pre-dose) and follow-up (Day 17 to Day 19)

    Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, QTcB, QTcF intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

  20. Change From Baseline in ECG Parameters for Part C

    Time frame: Baseline (Day -1) and Day 7 (pre-dose) and follow-up (Day 23)

    Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, QTcB, QTcF intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

  21. Number of Participants With Clinical Chemistry Data Outside the Range of Potential Clinical Importance (PCI) for Part A

    Time frame: Day 4 and follow up (Day 5 to Day 7)

    Clinical chemistry parameters assessed were alanine amino transferase (ALT), albumin (low <30 grams/liter), alkaline phosphatase, aspartate aminotransferase (AST), calcium (low <2 millimoles/liter and high >2.75 millimoles/liter), chloride, creatinine (high >159 micromoles/liter), direct bilirubin, gamma glutamyl transferase (GGT low <8 units/liter and high >78 units/liter), glucose (low <3 millimoles/liter and high >11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low <3 millimoles/liter and high >5.5 millimoles/liter), sodium (low <130 millimoles/liter and high >150 millimoles/liter), total bilirubin, total protein and urea/blood urea nitrogen (BUN). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

  22. Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A

    Time frame: Day 5, Day 7 and follow up (Day 9 to Day 11)

    Clinical chemistry parameters assessed were alanine amino transferase (ALT), albumin (low <30 grams/liter), alkaline phosphatase, AST, calcium (low <2 millimoles/liter and high >2.75 millimoles/liter), chloride, creatinine (high >159 micromoles/liter), direct bilirubin, GGT (low <8 units/liter and high >78 units/liter), glucose (low <3 millimoles/liter and high >11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low <3 millimoles/liter and high >5.5 millimoles/liter), sodium (low <130 millimoles/liter and high >150 millimoles/liter), total bilirubin, total protein and urea/BUN). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

  23. Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B

    Time frame: Day 3 and follow up (Day 17 to Day 19)

    Clinical chemistry parameters assessed were ALT, albumin (low <30 grams/liter), alkaline phosphatase, AST, calcium (low <2 millimoles/liter and high >2.75 millimoles/liter), chloride (low <98 millimoles/liter and high >106 millimoles/liter), creatinine (high >159 micromoles/liter), direct bilirubin, GGT (low <8 units/liter and high >78 units/liter), glucose (low <3 millimoles/liter and high >11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low <3 millimoles/liter and high >5.5 millimoles/liter), sodium (low <130 millimoles/liter and high >150 millimoles/liter), total bilirubin, total protein and urea/BUN (low <2.9 and high >7.1). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

  24. Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C

    Time frame: Day 1, Day 7 and follow up (Day 23)

    Clinical chemistry parameters assessed were ALT, albumin (low <30 grams/liter), alkaline phosphatase, AST, calcium (low <2 millimoles/liter and high >2.75 millimoles/liter), chloride (low <98 millimoles/liter and high >106 millimoles/liter), creatinine (high >159 micromoles/liter), direct bilirubin, GGT (low <8 units/liter and high >78 units/liter), glucose (low <3 millimoles/liter and high >11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low <3 millimoles/liter and high >5.5 millimoles/liter), sodium (low <130 millimoles/liter and high >150 millimoles/liter), total bilirubin, total protein (low <60 grams/liter and high >78 grams/liter) and urea/BUN (low <2.9 millimoles/liter and high >7.1 millimoles/liter). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

  25. Number of Participants With Hematology Data Outside the Range of PCI for Part A

    Time frame: Day 4 and follow up (Day 5 to Day 7)

    Hematology parameters assessed were basophils (high >0.1x10^9 cells/Liter), eosinophils (high >0.44x 10^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low <0.8x10^9 cells/Liter), mean corpuscle hemoglobin (MCH low <28 picograms and high >32 picograms), mean corpuscle hemoglobin concentration (MCHC low <32 grams/liter and high >36 grams/liter), mean corpuscle volume (MCV), monocytes (high >0.208x 10^9 cells/Liter), platelet count, red blood cell (RBC low <4.2x10^6 cells/microliter and high 5.9x10^6 cells/microliter) count, total neutrophils and white blood cell (WBC) count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

  26. Number of Participants With Hematology Data Outside the Range of PCI for Part A

    Time frame: Day 5, Day 7 and follow up (Day 9 to Day 11)

    Hematology parameters assessed were basophils (high >0.1x10^9 cells/Liter), eosinophils (high >0.44x 10^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low <0.8x10^9 cells/Liter), MCH (low <28 picograms and high >32 picograms), MCHC (low <32 grams/liter and high >36 grams/liter), MCV, monocytes (high >0.208x10^9 cells/Liter), platelet count, RBC count (low <4.2x10^6 cells/microliter and high 5.9x10^6 cells/microliter) count, total neutrophils, WBC count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

  27. Number of Participants With Hematology Data Outside the Range of PCI for Part B

    Time frame: Day 3 and follow up (Day 17 to 19)

    Hematology parameters assessed were basophils (high >0.1x10^9 cells/Liter), eosinophils (high >0.44x 10^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low <0.8x10^9 cells/Liter), MCH (low <28 picograms and high >32 picograms), MCHC (low <32 grams/liter and high >36 grams/liter), MCV, monocytes (high >0.208x10^9 cells/Liter), platelet count, RBC count (low <4.2x10^6 cells/microliter and high 5.9x10^6 cells/microliter) count, total neutrophils and WBC count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

  28. Number of Participants With Hematology Data Outside the Range of PCI for Part C

    Time frame: Day 1, Day 7 and follow up (Day 23)

    Hematology parameters assessed were basophils (high >0.1x10^9 cells/Liter), eosinophils (high >0.44x 10^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low <0.8x10^9 cells/Liter), MCH (low <28 picograms and high >32 picograms), MCHC low <32 grams/liter and high >36 grams/liter), MCV, monocytes (high >0.208x10^9 cells/Liter), platelet count, RBC count (low <4.2x10^6 cells/microliter and high 5.9x10^6 cells/microliter) count, total neutrophils and WBC count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

  29. Number of Participants With Tolerability Assessment for Part A

    Time frame: Up to Day 4

    Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed.

  30. Number of Participants With Tolerability Assessment for Part B

    Time frame: Up to Day 3

    Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed.

  31. Number of Participants With Tolerability Assessment for Part C

    Time frame: Up to Day 7

    Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed.

Secondary outcomes

  1. Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A

    Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours) and Day 3 (1,2,4,8,12,24 hours)

    Blood samples were collected to assess the plasma concentration of GSK2646264 for Part A on Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours) and Day 3 (1,2,4,8,12,24 hours). The actual date and time of each blood sample collection was recorded. PK Population comprised of all randomized participants of the Safety Population for whom a pharmacokinetic sample was obtained and analyzed.

  2. Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A

    Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours), Day 3 (1,2,4,8,12,24 hours) and Day 4 post-dose at Day 5 (30 and 36 hours), Day 6 (48,54 and 60 hours), Day 7 (72,78 and 84 hours) and Day 8 (96 hours)

    Blood samples were collected to assess the plasma concentration of GSK2646264 for Part A on Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours), Day 3 (1,2,4,8,12,24 hours) and Day 4 post-dose at Day 5 (30 and 36 hours), Day 6 (48,54 and 60 hours), Day 7 (72,78 and 84 hours) and Day 8 (96 hours). The actual date and time of each blood sample collection was recorded.

  3. Plasma GSK2646264 PK Concentrations for Part B

    Time frame: Day 1 (Pre-dose,1,4,8,12,24 hours), Day 2 (1,4,8,12,24 hours), Day 3 (1,4,8,12,24 hours), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to 19)

    Blood samples were collected to assess the plasma concentration of GSK2646264 for Part B on Day 1 (Pre-dose,1,4,8,12,24 hours), Day 2 (1,4,8,12,24 hours), Day 3 (1,4,8,12,24 hours), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to 19). The actual date and time of each blood sample collection was recorded.

  4. Plasma GSK2646264 PK Concentrations for Part C

    Time frame: Day 1 (Pre-dose,1 and 4 hours), Day 4 (Pre-dose and 4 hours), Day 7 (Pre-dose and 4 hours), Day 10, Day 15 and follow-up (Day 23)

    Blood samples were collected to assess the plasma concentration of GSK2646264 for Part C on Day 1 (Pre-dose,1 and 4 hours), Day 4 (Pre-dose and 4 hours), Day 7 (Pre-dose and 4 hours), Day 10, Day 15 and follow-up. The actual date and time of each blood sample collection was recorded.

  5. Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK2646264 for Part A

    Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-T) was determined using the currently approved and validated software.

  6. AUC (0-t) of GSK2646264 for Part A

    Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-T) was determined using the currently approved and validated software.

  7. Maximum Plasma Concentration (Cmax) of GSK2646264 for Part A

    Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.

  8. Cmax of GSK2646264 for Part A

    Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose

    Blood samples were collected at the indicated time points to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.

  9. Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK2646264 for Part A

    Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2,3 and 4

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-24) was determined using the currently approved and validated software. NA indicated data was not collected due to insufficient participants with data.

  10. Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK2646264 for Part A

    Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2,3 and 4

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-24) was determined using the currently approved and validated software.

  11. Time to Cmax (Tmax) of GSK2646264 for Part A

    Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3

    Blood samples were collected at the indicated time points to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.

  12. Tmax of GSK2646264 for Part A

    Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.

  13. Terminal Half-life (t1/2) of GSK2646264 for Part A

    Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2,3 and 4

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated t1/2 could not be calculated as we need at least 3 time points after Cmax within the same participant and this criteria could not be fulfilled due to lack of available data.

  14. t1/2 of GSK2646264 for Part A

    Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose at Day 5 (30 and 36 hours), Day 6 (48,54 and 60 hours), Day 7 (72,78 and 84 hours) and Day 8 (96 hours)

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated t1/2 could not be calculated as we need at least 3 time points after Cmax within the same participant and this criteria could not be fulfilled due to lack of available data.

  15. AUC [0-t] of GSK2646264 for Part B

    Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-t) was determined using the currently approved and validated software.

  16. Cmax of GSK2646264 for Part B

    Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 (Day 4)

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.

  17. AUC (0-24) of GSK2646264 for Part B

    Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 (Day 4)

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-24) was determined using the currently approved and validated software. NA indicates that geometric coefficient of variation could not be computed for Part B (3.5% BSA) GSK2646264 1% as a single participant was analyzed on Day 2.

  18. Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of GSK2646264 for Part B

    Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-infinity) was determined using the currently approved and validated software.

  19. Terminal Half-life (t1/2) of GSK2646264 for Part B

    Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software.

  20. Tmax of GSK2646264 for Part B

    Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.

  21. Cmax of GSK2646264 for Part C

    Time frame: Pre dose and 4 hours post-dose on Days 1, 4 and 7

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.

  22. Tmax of GSK2646264 for Part C

    Time frame: Pre dose and 4 hours post-dose on Days 1, 4 and 7

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.

  23. t1/2 of GSK2646264 for Part C

    Time frame: Pre dose and 4 hours post-dose on Days 1, 4 and 7

    Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated data was not collected due to insufficient number of participants with data to calculate half life.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

A Randomised Double Blind (Sponsor Unblinded), Single and Repeat Ascending Dose First Time in Human Study in Healthy Subjects, Cold Urticaria and Chronic Spontaneous Urticaria Subjects to Investigate Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of GSK2646264

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Apr 23, 2015
Registry last updated
Jun 21, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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