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NCT Number: NCT00538850

Fentanyl Sublingual Spray in Treating Patients With Breakthrough Cancer Pain

This is a phase III, randomized, double-blind, placebo-controlled, multicenter study of the clinical response to fentanyl sublingual spray as a treatment for breakthrough cancer pain. The study medication is administered under the tongue as a simple spray and can be self-administered by patients or assisted by their caregivers. Patients are titrated to an effective-dose of fentanyl sublingual spray in the open-label titration period and then proceed to the double-blind randomized period where they randomly receive 7 treatments with fentanyl sublingual spray and 3 treatments with placebo. Patients are treated for up to a total of 6-7 weeks (including both the open-label titration and the double-blind randomized periods).

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Key information

Conditions

Cancer Adenocarcinoma Adenoma Adenoma, Islet Cell Adnexal Diseases Adrenal Cortex Diseases Adrenal Cortex Neoplasms Adrenal Gland Diseases Adrenal Gland Neoplasms Adrenocortical Carcinoma Amyloidosis Anus Diseases Anus Neoplasms Appendiceal Neoplasms Astrocytoma Bile Duct Diseases Bile Duct Neoplasms Biliary Tract Diseases Biliary Tract Neoplasms Blast Crisis Blood Coagulation Disorders Blood Platelet Disorders Blood Protein Disorders Bone Marrow Diseases Bone Marrow Neoplasms Brain Diseases Brain Neoplasms Breast Carcinoma In Situ Breast Diseases Breast Neoplasms Breast Neoplasms, Male Bronchial Neoplasms Burkitt Lymphoma Carcinogenesis Carcinoma Carcinoma in Situ Carcinoma, Bronchogenic Carcinoma, Hepatocellular Carcinoma, Islet Cell Carcinoma, Neuroendocrine Carcinoma, Non-Small-Cell Lung Carcinoma, Ovarian Epithelial Carcinoma, Renal Cell Carcinoma, Squamous Cell Cardiovascular Diseases Cecal Diseases Cecal Neoplasms Cell Transformation, Neoplastic Central Nervous System Diseases Central Nervous System Neoplasms Cerebral Ventricle Neoplasms Chondrosarcoma Choroid Plexus Neoplasms Chronic Disease Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cranial Nerve Diseases Craniopharyngioma DNA Virus Infections Desmoid Tumors Digestive System Diseases Digestive System Neoplasms Disease Attributes Endocrine Gland Neoplasms Endocrine System Diseases Endometrial Neoplasms Ependymoma Epstein-Barr Virus Infections Esophageal Diseases Esophageal Neoplasms Esthesioneuroblastoma, Olfactory Eye Neoplasms Fallopian Tube Diseases Fallopian Tube Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Fibroma Gallbladder Diseases Gallbladder Neoplasms Gastrinoma Gastrointestinal Diseases Gastrointestinal Neoplasms Gastrointestinal Stromal Tumors Genital Diseases Genital Diseases, Female Genital Diseases, Male Genital Neoplasms, Female Genital Neoplasms, Male Glioblastoma Glioma Glioma, Subependymal Gliosarcoma Glucagonoma Gonadal Disorders Head and Neck Neoplasms Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Herpesviridae Infections Hodgkin Disease Hypergammaglobulinemia Immune System Diseases Immunoblastic Lymphadenopathy Immunoglobulin Light-chain Amyloidosis Immunoproliferative Disorders Infections Insulinoma Intestinal Diseases Intestinal Neoplasms Intraocular Lymphoma Kidney Diseases Kidney Neoplasms Leukemia Leukemia, B-Cell Leukemia, Biphenotypic, Acute Leukemia, Hairy Cell Leukemia, Large Granular Lymphocytic Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Leukemia, Myeloid, Accelerated Phase Leukemia, Myeloid, Acute Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative Leukemia, Myeloid, Chronic-Phase Leukemia, Myelomonocytic, Chronic Leukemia, Neutrophilic, Chronic Leukemia, Prolymphocytic Leukemia, T-Cell Liver Diseases Liver Neoplasms Lung Diseases Lung Neoplasms Lymphadenopathy Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Anaplastic Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoproliferative Disorders Male Urogenital Diseases Medulloblastoma Melanoma Meningeal Neoplasms Meningioma Mesothelioma Mesothelioma, Malignant Metabolic Diseases Monoclonal Gammopathy of Undetermined Significance Mouth Diseases Mouth Neoplasms Multiple Myeloma Mycosis Fungoides Myelodysplastic-Myeloproliferative Diseases Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Bone Tissue Neoplasms, Complex and Mixed Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Fibrous Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neoplasms, Plasma Cell Neoplasms, Vascular Tissue Neoplastic Processes Nephroma, Mesoblastic Nervous System Diseases Nervous System Neoplasms Neuroblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Neuroectodermal Tumors, Primitive, Peripheral Neuroendocrine Tumors Neurologic Manifestations Nevi and Melanomas Nutritional and Metabolic Diseases Olfactory Nerve Diseases Oligodendroglioma Osteosarcoma Ovarian Diseases Ovarian Neoplasms Pain Pancreatic Diseases Pancreatic Neoplasms Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Pdgfra-Associated Chronic Eosinophilic Leukemia Penile Diseases Penile Neoplasms Pinealoma Pleural Neoplasms Polycythemia Vera Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Primary Myelofibrosis Prostatic Diseases Prostatic Neoplasms Proteostasis Deficiencies Rectal Diseases Rectal Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Salivary Gland Diseases Salivary Gland Neoplasms Sarcoma Sezary Syndrome Signs and Symptoms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Small Cell Lung Carcinoma Somatostatinoma Squamous Cell Carcinoma of Head and Neck Stomach Diseases Stomach Neoplasms Stomatognathic Diseases Testicular Diseases Testicular Neoplasms Thoracic Neoplasms Thrombocythemia, Essential Thrombocytosis Thymoma Thymus Neoplasms Tumor Virus Infections Urethral Diseases Urethral Neoplasms Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Uterine Cervical Diseases Uterine Cervical Neoplasms Uterine Diseases Uterine Neoplasms Vaginal Diseases Vaginal Neoplasms Vascular Diseases Vipoma Virus Diseases Vulvar Diseases Vulvar Neoplasms Waldenstrom Macroglobulinemia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

InSys Therapeutics, Incorporated

Chandler, Arizona, 85224, United States

About this study

RATIONALE

Fentanyl sublingual spray may help relieve breakthrough pain in patients receiving opioids for cancer pain.

OBJECTIVES

Primary

  • Determine the efficacy and safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain in patients on around-the-clock opioids for their persistent cancer pain.

Secondary

  • Evaluate the safety of fentanyl sublingual spray in these opioid-tolerant patients.
  • Assess the patient's satisfaction with treatment medication.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Male or female, ≥ 18 years of age.
  • Diagnosis of cancer.
  • Opioid-tolerant. Subjects who were opioid tolerant were those taking ≥ 60 mg of oral morphine/day, at least 25 μg of transdermal fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer for cancer-related pain.
  • Experienced persistent pain related to the cancer or its treatment of moderate or lesser intensity in the 24 hours prior to assessment by a verbal rating scale at the Screening Visit.
  • Over the previous 7 days, subject experienced, on average, 1 to 4 breakthrough cancer pain episodes per day usually at least partially controlled by supplemental medication of at least 5 mg immediate-release morphine or an equivalent short-acting opioid (eg, oxycodone, hydrocodone, or codeine with acetaminophen).
  • Able to evaluate and record pain relief, assess medication performance at set times after dosing, record AEs, record each use of the study drug or supplemental medication in an electronic diary (a caregiver may have provided the subject the medication, help with the mechanics of handling the electronic diary but was not permitted to record any information in the electronic diary).
  • Able and willing to give informed consent.
  • Women of childbearing potential were to have a) a negative serum pregnancy test, b) not be breastfeeding and c) agree to practice a reliable form of contraception.

Exclusion criteria

  • Intolerance to opioids or fentanyl.
  • Current use of commercially available oral short-acting fentanyl for breakthrough pain. Subjects previously on Actiq or Fentora were permitted to be enrolled if they had a 7 day washout.
  • Rapidly increasing/uncontrolled pain.
  • A history of major organ system impairment or disease, that in the Investigator's or his/her designee's opinion could increase the risk associated with the use of opioids.
  • Uncontrolled hypertension (systolic blood pressure {SBP} > 180 mmHg or diastolic blood pressure [DBP] > 90 mmHg on 2 occasions ≥ 6 hours apart) despite antihypertensive therapy, or a history of hypertensive crisis within the past 2 years.
  • A recent history (≤ 2 years prior) of transient ischemic attacks, neural vascular disease, stroke, or cerebral aneurysms.
  • Clinically uncontrolled sleep apnea.
  • Brain metastases with signs or symptoms of increased intracranial pressure.
  • Inability to assess pain or response to pain medications for any reason, including psychiatric disorder, concurrent medical disorder, or concomitant therapy.
  • Received investigational study product(s) ≤ 30 days prior to the Screening Visit.
  • Painful erythema, oedema or ulcers under the tongue.
  • Use of monoamine oxidase (MAO) inhibitors within 14 days of the Screening Visit.

Treatment and study plan

Fentanyl sublingual spray

Drug

In the open-label titration period of the study, participants started at a dose of 100, 200, or 400 µg and titrated upward to a maximum dose of 1600 µg. Titration was stopped when the dose administered provided adequate analgesia for breakthrough pain without unacceptable side effects or the maximum titration period of 21±5 days was reached. In the double-blind period of the study, participants received fentanyl sublingual spray in doses of 100, 200, 400, 600, 800, 1200, or 1600 µg determined in the open-label titration period of the study.

Other names: SUBSYS

Placebo

Drug

Matching placebo to fentanyl sublingual spray.

Primary outcomes

  1. Summed Pain Intensity Differences (SPID) at 30 Minutes After Dosing (SPID30)

    Time frame: Baseline (time 0, beginning of each pain episode) through 30 minutes after dosing for each pain episode

    Pain intensity was assessed by the participant using a 0-100 mm visual analog scale where 0 represented "no pain" and 100 represented "worst possible pain" at 0 (baseline, beginning of the pain episode), 5, 10, 15, and 30 minutes after each dose of study medication during each breakthrough pain episode. The pain intensity difference was defined as the difference in pain intensity at the various time points versus time 0 (baseline). SPID30 was calculated as the time-weighted sum of the PID scores using the following formula: SPID30=(5*PID5)+(5*PID10)+(5*PID15)+(15*PID30). The minimum and maximum SPID30 scores were -3000 and 3000. A higher score indicates less pain.

Secondary outcomes

  1. Summed Pain Intensity Differences (SPID) at 5, 10, 15, 45, and 60 Minutes After Dosing

    Time frame: Baseline (time 0, beginning of each pain episode) through 60 minutes after dosing for each pain episode

    Pain intensity was assessed by the participant using a 0-100 mm visual analog scale where 0 represented "no pain" and 100 represented "worst possible pain" at 0 (baseline, beginning of the pain episode), 5, 10, 15, 30, 45 and 60 minutes after each dose of study medication during each breakthrough pain episode. The pain intensity difference was defined as the difference in pain intensity at the various time points versus time 0 (baseline). SPID was calculated as the time-weighted sum of the PID scores using the following formulas: SPID5=(5*PID5), SPID10=(5*PID5)+(5*PID10), SPID15=(5*PID5)+(5*PID10)+(5*PID15), SPID30=(5*PID5)+(5*PID10)+(5*PID15)+(15*PID30), SPID45=(5*PID5)+(5*PID10)+(5*PID15)+(15*PID30)+(15*PID45), SPID60=(5*PID5)+(5*PID10)+(5*PID15)+(15*PID30) +(15*PID45) +(15*PID60). The minimum and maximum SPID scores were -500 to 500, -1000 to 1000, -1500 to 1500, -3000 to 3000, -4500 to 4500, and -6000 to 6000, respectively. A higher score indicates less pain.

  2. Total Pain Relief (TOTPAR) at 5, 10, 15, 30, 45, and 60 Minutes After Dosing

    Time frame: 5 through 60 minutes after dosing for each pain episode

    Pain relief (PAR) was assessed by the participant on a 5-point scale (1=No relief, 2=A little relief, 3=Moderate relief, 4=A lot of relief, 5=Complete relief) at 5, 10, 15, 30, 45 and 60 minutes after each dose of study medication during each breakthrough pain episode. TOTPAR was calculated as the time-weighted sum of the PAR scores at each time point using the following formulas: TOTPAR5=(5*PAR5), TOTPAR10=(5*PAR5)+(5*PAR10), TOTPAR15=(5*PAR5)+(5*PAR10)+(5*PAR15), TOTPAR30=(5*PAR5)+(5*PAR10)+(5*PAR15)+(15*PAR30), TOTPAR45=(5*PAR5)+(5*PAR10)+(5*PAR15)+(15*PAR30)+(15*PAR45), TOTPAR60=(5*PAR5)+(5*PAR10)+(5*PAR15)+(15*PAR30) +(15*PAR45) +(15*PAR60). The minimum and maximum TOTPAR5, TOTPAR10, TOTPAR15, TOTPAR30, TOTPAR45, and TOTPAR60 scores were 5 to 25, 10 to 50, 15 to 75, 30 to 150, 45 to 225, and 60 to 300, respectively. A higher score indicates more pain relief.

  3. Global Evaluation of the Study Medication at 30 and 60 Minutes After Dosing

    Time frame: 30 through 60 minutes after dosing for each pain episode

    Global evaluation of the study medication was assessed by the participant on a 5-point scale (1=Poor, 2=Fair, 3=Good, 4=Very good, 5=Excellent) at 30 and 60 minutes after each dose of study medication during each breakthrough pain episode. A higher score indicates a better evaluation.

Sponsors and collaborators

Lead sponsor

INSYS Therapeutics Inc

Industry

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

A Randomized, Double-blind, Placebo-controlled Multi-center Study to Evaluate the Safety and Efficacy of Fentanyl Sublingual Spray (Fentanyl SL Spray) for the Treatment of Breakthrough Cancer Pain

Important dates

Study start
2007
Primary completion
2010
Study completion
2010
First posted
Oct 3, 2007
Registry last updated
Mar 5, 2014

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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