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Completed

NCT Number: NCT03919890

A Two-Part Study to Assess the Safety, Tolerability, PK and PD of ONO-7684 in Healthy Adult Volunteers

This is a first in human study to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of ONO-7684 in healthy adult volunteers. This study will be conducted in 2 parts: Part A is a single-ascending dose and Part B is a multiple-ascending dose.

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Key information

Conditions

Venous Thromboembolism Cardiovascular Diseases Embolism and Thrombosis Thromboembolism Vascular Diseases

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Hammersmith Medicines Research (HMR)

London, NW10 7EW, United Kingdom

About this study

This study aims to obtain safety, tolerability, pharmacokinetic and pharmacodynamic data when ONO-7684 is administered orally as single doses and as multiple doses to healthy subjects. The study will consist of 2 parts: A single ascending dose (SAD) phase (Part A); a multiple ascending dose (MAD) phase (Part B). One cohort of Part A will receive ONO-7684 under both fasted and fed conditions to investigate the effect of food.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • 18-55 years
  • normotensive male volunteers, or female volunteers of non-childbearing potential (Part B only)
  • body mass index 18.0-30.0 kg/m2
  • deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine
  • registered with a General Practitioner (GP) in the UK
  • agree to use an effective method of contraception
  • able to give fully informed written consent

Exclusion criteria

  • Positive tests for hepatitis B & C, HIV
  • severe adverse reaction to any drug
  • sensitivity to trial medication
  • drug or alcohol abuse
  • current smoker or use of nicotine containing products in the previous 6 months
  • vegetarians or vegans, or unwilling to eat a high-fat breakfast (Part A food effect cohorts only)
  • use of strong CYP3A4/5 or P-glycoprotein inhibitors or inducers, anticoagulants, antiplatelet agents, non-steroidal anti-inflammatory drugs and/or acetylsalicylic acid within the previous 30 days
  • prescription or over-the-counter medication, vitamins, herbal treatments or dietary supplements within the previous 7 days (with the exception of paracetamol [acetaminophen])
  • participation in other clinical trials of unlicensed medicines, or loss of more than 400 mL blood, within the previous 3 months or plan to donate blood or blood products in the 3 months after the trial
  • vital signs outside the acceptable range
  • clinically relevant abnormal findings at the screening assessment (including creatinine clearance, haemoglobin levels and QTcF)
  • acute or chronic illness
  • clinically relevant abnormal medical history or concurrent medical condition
  • objection by GP
  • possibility that volunteer will not cooperate
  • pre-menopausal females who are pregnant or lactating, or who are of childbearing potential

Treatment and study plan

ONO-7684

Drug

Single ascending doses for cohorts A1-A8 and multiple ascending doses cohorts B1-3

ONO-7684 Placebo

Drug

Placebo comparator

Primary outcomes

  1. Number of participants with clinically significant changes in vital signs (Part A & B)

    Time frame: Part A: Day 1-4 & Follow-up and Part B: Day 1-15, 17 & Follow up

    Pulse rate (bpm), systolic and diastolic blood pressure (mmHg), Respiratory rate (bpm)

  2. Number of participants with clinically significant changes observed on 12-lead electrocardiogram (ECG) (Part A & B)

    Time frame: Part A: Day 1-4 & Follow up & Part B: Day 1,3,5,7,9,11,14,17 & Follow up

    Ventricular rate (beats/min), PR interval (msec), QRS interval (msec), QT (msec), QTcF interval (msec)

  3. Number of participants with clinically significant changes in cardiac telemetry (Part A only)

    Time frame: Part A: From 0.5-1 hours pre-dose until 12 hours after dosing at Day 1

    Number of participants with cardiac telemetry abnormalities will be reported.

  4. Number of participants with clinically significant changes in physical examination (Part A & B)

    Time frame: Part A: Day -1, 1-4 & Follow-up and Part B: Day-1, 1-17 & Follow up

    Number of participants with physical examination abnormalities will be reported.

  5. Number of participants with clinically significant changes in laboratory safety tests (haematology, biochemistry and urinalysis) (Part A & B)

    Time frame: Part A: Day-1, 1-4 & Follow up and Part B: Day-1, 1-17 & Follow up

    Number of participants with abnormalities in laboratory safety tests will be reported.

  6. Number of participants with adverse events (AE) (Part A & B)

    Time frame: Part A: Day-1, 1-4 & Follow up and Part B: Day-1, 1-17 & Follow up

    AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Secondary outcomes

  1. Pharmacokinetics (Cmax)

    Time frame: Part A: Day 1 through Day 4. Part B: Day 1 and Day 14

    Assessment of the maximum observed plasma concentration of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B

  2. Pharmacokinetics (tmax)

    Time frame: Part A: Day 1 through Day 4. Part B: Day 1 and Day 14

    Assessment of the maximum observed plasma concentration of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B

  3. Pharmacokinetics (AUClast)

    Time frame: Part A: Day 1 through Day 4. Part B: Day 14

    Assessment of the area under the curve of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B

  4. Pharmacokinetics (AUCinf)

    Time frame: Part A: Day 1 through Day 4. Part B: Day 14

    Assessment of the area under the curve of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B

  5. Pharmacokinetics (AUCt)

    Time frame: Part A: Day 1 through Day 4. Part B: Day 1

    Assessment of the area under the curve of concentration of ONO-7684 and 3-hydroxybenzoic acid - time from zero up to a definitive time, t in Parts A and B

  6. Pharmacokinetics (%AUCextrap)

    Time frame: Part A: Day 1 through Day 4. Part B: Day 14

    Assessment of the percentage of AUC∞ extrapolated from tlast to infinity of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B

  7. Pharmacokinetics (t1/2)

    Time frame: Part A: Day 1 through Day 4. Part B: Day 14

    Assessment of the elimination half-time of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B

  8. Pharmacokinetics (CL/F)

    Time frame: Day 1 through Day 4

    Assessment of the apparent clearance rate of ONO-7684 and 3-hydroxybenzoic acid in Part A only

  9. Pharmacokinetics (Terminal Rate Constant)

    Time frame: Day 1 through Day 4

    Assessment of the terminal rate constant (slowest rate constant of the disposition) of ONO-7684 and 3-hydroxybenzoic acid in plasma in Part A only

  10. Pharmacokinetics (Aet)

    Time frame: Day 1 through Day 4

    Assessment of the amount of ONO-7684 excreted in urine over the period of sample collection in Part A only

  11. Pharmacokinetic (fe/F)

    Time frame: Day 1 through Day 4

    Assessment of the fraction of orally administered ONO-7684 excreted into urine in Part A only

  12. Pharmacokinetic (CLr)

    Time frame: Day 1 through Day 4

    Assessment of the renal clearance of ONO-7684 from plasma in Part A only

  13. Pharmacokinetic (Ctrough)

    Time frame: Day 1 through Day 14

    Assessment of the trough plasma concentration of ONO-7684 and 3-hydroxybenzoic acid in Part B only

  14. Pharmacokinetic (AUCtau)

    Time frame: Day 14

    Assessment of the area under the plasma concentration of ONO-7684 and 3-hydroxybenzoic acid -time during a dosing interval in Part B only

  15. Pharmacokinetic (CLSS/F)

    Time frame: Day 14

    Assessment of total clearance of ONO-7684 from plasma after oral administration in Part B only

  16. Pharmacokinetic (VZ/F)

    Time frame: Day 14

    Assessment of apparent volume of distribution of ONO-7684 after non-intravenous administration calculated at steady state in Part B only

  17. Pharmacodynamic (change from baseline in aPTT activity) in serum

    Time frame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17

    Assessment of the effect of ONO-7684 in activated partial thromboplastin time in Parts A and B

  18. Pharmacodynamic (change from baseline in PT activity) in serum

    Time frame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17

    Assessment of the effect of ONO-7684 in prothrombin time in Parts A and B

  19. Pharmacodynamic (change from baseline in PT-INR activity) in serum

    Time frame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17

    Assessment of the effect of ONO-7684 in prothrombin time-international normalised ratio in Parts A and B

  20. Pharmacodynamic (change from baseline in FXIa activity) in serum

    Time frame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17

    Assessment of the effect of ONO-7684 in blood coagulation activated factor XI in Parts A and B

  21. Pharmacodynamic (correlation of aPTT and FXIa activity) in serum

    Time frame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17

    Assessment of the effect of ONO-7684 in the correlation of activated partial thromboplastin time to blood coagulation activated factor XI in Parts A and B

Sponsors and collaborators

Lead sponsor

Ono Pharmaceutical Co., Ltd.

Industry

Registry information

Official study title

A First-in-human, Randomised, Placebo-controlled, Double-blind, Single and Multiple Dose Study to Explore the Safety, Tolerability, PK and PD of Oral Doses of ONO-7684 in Healthy Subjects Under Fed and Fasted Conditions

Important dates

Study start
2019
Primary completion
2019
Study completion
2019
First posted
Apr 18, 2019
Registry last updated
Dec 9, 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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