Fentanyl Sublingual Spray in Treating Patients With Breakthrough Cancer Pain

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
INSYS Therapeutics Inc
ClinicalTrials.gov Identifier:
NCT00538850
First received: October 1, 2007
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
Cancer
Drug: Fentanyl sublingual spray
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Malignant Mesenchymal Tumor Soft Tissue Sarcoma Lymphoma, Small Cleaved-cell, Diffuse Fallopian Tube Cancer Ovarian Epithelial Cancer Multiple Myeloma Chronic Myeloproliferative Disorders Small Intestine Cancer Glioblastoma Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Acute Lymphoblastic Leukemia Testicular Cancer Hodgkin Lymphoma Esophageal Cancer Waldenstrom Macroglobulinemia Stomach Carcinoma Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic/myeloproliferative Disease Uterine Sarcoma Pancreatic Cancer Acute Myeloid Leukemia, Adult Follicular Lymphoma Vaginal Cancer Liver Cancer Supratentorial Primitive Neuroectodermal Tumor B-cell Lymphomas Nasopharyngeal Carcinoma Myelofibrosis Metastatic Squamous Neck Cancer With Occult Primary Glioma Burkitt Lymphoma Craniopharyngioma Ependymoma Lymphoma, Large-cell Lymphomatoid Granulomatosis Medulloblastoma Meningioma Oligodendroglioma Anaplastic Oligodendroglioma Lymphoma, Large-cell, Immunoblastic Lymphoblastic Lymphoma Subependymal Giant Cell Astrocytoma Pineoblastoma Neuroepithelioma Anaplastic Large Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Osteosarcoma Bone Cancer Ewing's Sarcoma Ewing's Family of Tumors Kidney Cancer Renal Cancer Chronic Myelomonocytic Leukemia Chronic Neutrophilic Leukemia Hypereosinophilic Syndrome Gastrointestinal Stromal Tumors Monoclonal Gammopathy of Undetermined Significance Laryngeal Cancer Hypopharyngeal Cancer Central Nervous System Lymphoma, Primary Urethral Cancer Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Breast Cancer, Male AL Amyloidosis Pilocytic Astrocytoma Gliosarcoma Brain Tumor, Adult Leiomyosarcoma Anaplastic Astrocytoma Chondrosarcoma Malignant Mesothelioma Leukemia, T-cell, Chronic Rhabdoid Tumor Adrenocortical Carcinoma Anal Cancer Vulvar Cancer Essential Thrombocythemia Bile Duct Cancer Ovarian Germ Cell Tumor Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Hairy Cell Leukemia Mycosis Fungoides Sezary Syndrome Large Granular Lymphocyte Leukemia Intrahepatic Cholangiocarcinoma Extragonadal Germ Cell Tumor Anaplastic Plasmacytoma Gall Bladder Cancer Acinic Cell Carcinoma Polycythemia Vera Hemangiopericytoma Pineocytoma Diffuse Astrocytoma Anaplastic Ependymoma Embryonal Tumor With Multilayered Rosettes Adenoid Cystic Carcinoma Pancreatic Islet Cell Tumors Carcinoid Tumor Mucoepidermoid Carcinoma Insulinoma Zollinger-Ellison Syndrome Glucagonoma Glucagonoma Syndrome Somatostatinoma WDHA Syndrome Desmoid Tumor Myxopapillary Ependymoma Subependymoma Esthesioneuroblastoma Midline Lethal Granuloma Congenital Mesoblastic Nephroma
U.S. FDA Resources

Further study details as provided by INSYS Therapeutics Inc:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 130
Study Start Date: October 2007
Study Completion Date: October 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fentanyl sublingual spray
Participants received fentanyl sublingual spray 7 times or placebo 3 times in random order to treat up to a maximum of 2 breakthrough pain episodes per day with a minimum separation of 2 hours between treatments. Patients received a dose of 100 to 1600 µg determined in the open-label dose titration period of the current study.
Drug: Fentanyl sublingual spray
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 Name: SUBSYS
Drug: Placebo
Matching placebo to fentanyl sublingual spray.

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00538850

Locations
United States, Arizona
InSys Therapeutics, Incorporated
Chandler, Arizona, United States, 85224
Sponsors and Collaborators
INSYS Therapeutics Inc
Investigators
Study Chair: Larry Dillaha, MD INSYS Therapeutics Inc
  More Information

Additional Information:
Publications:
Responsible Party: INSYS Therapeutics Inc
ClinicalTrials.gov Identifier: NCT00538850     History of Changes
Obsolete Identifiers: NCT00589342
Other Study ID Numbers: INS-05-001, CDR0000581128
Study First Received: October 1, 2007
Results First Received: May 8, 2013
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by INSYS Therapeutics Inc:
unspecified adult solid tumor, protocol specific
pain
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
stage IV chronic lymphocytic leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic myelomonocytic leukemia
chronic phase chronic myelogenous leukemia
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Fentanyl
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Intravenous
Anesthetics, General
Anesthetics

ClinicalTrials.gov processed this record on April 16, 2014