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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:

MedlinePlus related topics: Cancer
Genetic and Rare Diseases Information Center resources: AL Amyloidosis Acinic Cell Carcinoma Acute Lymphoblastic Leukemia Acute Myelocytic Leukemia Acute Myeloid Leukemia, Adult Acute Non Lymphoblastic Leukemia Adenoid Cystic Carcinoma Adrenocortical Carcinoma Anal Cancer Anaplastic Astrocytoma Anaplastic Ependymoma Anaplastic Large Cell Lymphoma Anaplastic Oligodendroglioma Anaplastic Plasmacytoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Angioimmunoblastic T-cell Lymphoma B-cell Lymphomas Bile Duct Cancer Bone Cancer Brain Tumor, Adult Breast Cancer, Male Burkitt Lymphoma Carcinoid Tumor Central Nervous System Lymphoma, Primary Chondrosarcoma Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Myelomonocytic Leukemia Chronic Myeloproliferative Disorders Chronic Neutrophilic Leukemia Congenital Mesoblastic Nephroma Craniopharyngioma Cutaneous T-cell Lymphoma Desmoid Tumor Diffuse Astrocytoma Embryonal Tumor With Multilayered Rosettes Ependymoma Esophageal Cancer Essential Thrombocythemia Esthesioneuroblastoma Ewing's Family of Tumors Ewing's Sarcoma Extragonadal Germ Cell Tumor Fallopian Tube Cancer Follicular Lymphoma Gall Bladder Cancer Gastrointestinal Stromal Tumors Glioblastoma Glioma Gliosarcoma Glucagonoma Glucagonoma Syndrome Hairy Cell Leukemia Hemangiopericytoma Hodgkin Lymphoma Hypereosinophilic Syndrome Hypopharyngeal Cancer Insulinoma Intrahepatic Cholangiocarcinoma Kidney Cancer Large Granular Lymphocyte Leukemia Laryngeal Cancer Leiomyosarcoma Leukemia, B-cell, Chronic Leukemia, Myeloid Leukemia, T-cell, Chronic Liver Cancer Lymphoblastic Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoma, Small Cleaved-cell, Diffuse Lymphomatoid Granulomatosis Lymphosarcoma Malignant Mesenchymal Tumor Malignant Mesothelioma Mantle Cell Lymphoma Medulloblastoma Meningioma Metastatic Squamous Neck Cancer With Occult Primary Midline Lethal Granuloma Monoclonal Gammopathy of Undetermined Significance Mucoepidermoid Carcinoma Multiple Myeloma Mycosis Fungoides Myelodysplastic Syndromes Myelodysplastic/myeloproliferative Disease Myelofibrosis Myxopapillary Ependymoma Nasopharyngeal Carcinoma Neuroepithelioma Oligodendroglioma Osteosarcoma Ovarian Epithelial Cancer Ovarian Germ Cell Tumor Pancreatic Cancer Pancreatic Islet Cell Tumors Pilocytic Astrocytoma Pineoblastoma Pineocytoma Plasmablastic Lymphoma Polycythemia Vera Renal Cancer Rhabdoid Tumor Sezary Syndrome Small Intestine Cancer Soft Tissue Sarcoma Somatostatinoma Stomach Carcinoma Subependymal Giant Cell Astrocytoma Subependymoma Supratentorial Primitive Neuroectodermal Tumor Testicular Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter Urethral Cancer Uterine Sarcoma Vaginal Cancer Vulvar Cancer WDHA Syndrome Waldenstrom Macroglobulinemia Zollinger-Ellison Syndrome
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
salivary gland acinic cell tumor
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

Additional relevant MeSH terms:
Fentanyl
Adjuvants, Anesthesia
Analgesics
Analgesics, Opioid
Anesthetics
Anesthetics, General
Anesthetics, Intravenous
Central Nervous System Agents
Central Nervous System Depressants
Narcotics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014