Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Long-term Safety and Efficacy Study of Fentanyl Sublingual Spray for the Treatment of Breakthrough Cancer Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00538863
Recruitment Status : Completed
First Posted : October 3, 2007
Results First Posted : October 11, 2013
Last Update Posted : October 11, 2013
Sponsor:
Information provided by (Responsible Party):
INSYS Therapeutics Inc

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Supportive Care
Conditions Cancer
Pain
Intervention Drug: Fentanyl sublingual spray
Enrollment 319
Recruitment Details The number of patients in the fentanyl sublingual spray maintenance group includes 179 patients who completed the fentanyl sublingual spray titration period of the study plus 90 patients who entered the study directly in the maintenance period.
Pre-assignment Details Five patients who completed the titration period did not start the maintenance period due to failure to determine a dose in the titration period (n=1), withdrawal from the study (n=3), and adverse event (n=1).
Arm/Group Title Fentanyl Sublingual Spray
Hide Arm/Group Description In the titration period, patients were titrated upward to a maximum dose of 1600 µg fentanyl sublingual spray. In the maintenance period, patients received a dose of 100 to 1600 µg fentanyl sublingual spray determined in a previous study (INS-05-001, NCT00538850) or in the titration period of the current study.
Period Title: Open-label Titration
Started 229
Completed 184
Not Completed 45
Period Title: Open-label Maintenance
Started 269 [1]
Completed 163
Not Completed 106
[1]
Five participants who completed the titration period did not start the maintenance period.
Arm/Group Title Fentanyl Sublingual Spray
Hide Arm/Group Description In the titration period, patients were titrated upward to a maximum dose of 1600 µg fentanyl sublingual spray. In the maintenance period, patients received a dose of 100 to 1600 µg fentanyl sublingual spray determined in a previous study (INS-05-001, NCT00538850) or in the titration period of the current study.
Overall Number of Baseline Participants 319
Hide Baseline Analysis Population Description
The total number of patients enrolled in the study is 319.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 319 participants
Titration Period 54.1  (12.5)
Maintenance Period 53.6  (12.2)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 319 participants
Titration period - Female 117
Titration period - Male 112
Maintenance period - Female 141
Maintenance period - Male 128
1.Primary Outcome
Title Percentage of Patients That Experienced 1 or More Adverse Events
Hide Description [Not Specified]
Time Frame Baseline to end of the study (up to 116 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: All patients who received study medication.
Arm/Group Title Fentanyl Sublingual Spray Titration Fentanyl Sublingual Spray Maintenance
Hide Arm/Group Description:
Patients received fentanyl sublingual spray to treat up to a maximum of 4 breakthrough pain episodes per day with a minimum separation of 4 hours between treatments. Patients 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 26 days was reached.
Patients received fentanyl sublingual spray up to a maximum of 4 times per day with a minimum separation of 4 hours between treatments for 90 days. Patients received a dose of 100 to 1600 µg determined in a previous study (INS-05-001, NCT00538850) or in the open-label dose titration period of the current study. The dose administered provided adequate analgesia for breakthrough pain without unacceptable side effects.
Overall Number of Participants Analyzed 229 269
Measure Type: Number
Unit of Measure: Percentage of patients
59.0 80.7
Time Frame All adverse events were followed to resolution, an outcome had been reached, stabilization, or the event was otherwise explained regardless of whether the subject was still participating in the study (up to 150 days).
Adverse Event Reporting Description Safety population: All patients (n=319) who received study medication. The number of patients in the fentanyl sublingual spray maintenance group includes 179 patients who completed the fentanyl sublingual spray titration period of the study plus 90 patients who entered the study directly in the maintenance period.
 
Arm/Group Title Fentanyl Sublingual Spray Titration Fentanyl Sublingual Spray Maintenance
Hide Arm/Group Description Patients received fentanyl sublingual spray to treat up to a maximum of 4 breakthrough pain episodes per day with a minimum separation of 4 hours between treatments. Patients 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 26 days was reached. Patients received fentanyl sublingual spray up to a maximum of 4 times per day with a minimum separation of 4 hours between treatments for 90 days. Patients received a dose of 100 to 1600 µg determined in a previous study (INS-05-001, NCT00538850) or in the open-label dose titration period of the current study. The dose administered provided adequate analgesia for breakthrough pain without unacceptable side effects.
All-Cause Mortality
Fentanyl Sublingual Spray Titration Fentanyl Sublingual Spray Maintenance
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Fentanyl Sublingual Spray Titration Fentanyl Sublingual Spray Maintenance
Affected / at Risk (%) Affected / at Risk (%)
Total   33/229 (14.41%)   178/269 (66.17%) 
Blood and lymphatic system disorders     
Anaemia  1  0/229 (0.00%)  4/269 (1.49%) 
Neutropenia  1  0/229 (0.00%)  1/269 (0.37%) 
Pancytopenia  1  0/229 (0.00%)  1/269 (0.37%) 
Thrombocytopenia  1  0/229 (0.00%)  2/269 (0.74%) 
Cardiac disorders     
Cardiac failure congestive  1  1/229 (0.44%)  0/269 (0.00%) 
Arrhythmia  1  0/229 (0.00%)  1/269 (0.37%) 
Atrial fibrillation  1  0/229 (0.00%)  1/269 (0.37%) 
Cardiac failure  1  0/229 (0.00%)  1/269 (0.37%) 
Cardio-respiratory arrest  1  0/229 (0.00%)  1/269 (0.37%) 
Cardiopulmonary failure  1  0/229 (0.00%)  1/269 (0.37%) 
Congenital, familial and genetic disorders     
Pyloric stenosis  1  0/229 (0.00%)  1/269 (0.37%) 
Gastrointestinal disorders     
Abdominal pain  1  1/229 (0.44%)  2/269 (0.74%) 
Ascites  1  1/229 (0.44%)  0/269 (0.00%) 
Nausea  1  1/229 (0.44%)  3/269 (1.12%) 
Pancreatitis  1  1/229 (0.44%)  0/269 (0.00%) 
Vomiting  1  2/229 (0.87%)  3/269 (1.12%) 
Abdominal distension  1  0/229 (0.00%)  1/269 (0.37%) 
Diarrhoea  1  0/229 (0.00%)  2/269 (0.74%) 
Dysphagia  1  0/229 (0.00%)  1/269 (0.37%) 
Gastritis  1  0/229 (0.00%)  2/269 (0.74%) 
Gastrointestinal fistula  1  0/229 (0.00%)  1/269 (0.37%) 
Gastrointestinal haemorrhage  1  0/229 (0.00%)  1/269 (0.37%) 
Glossitis  1  0/229 (0.00%)  1/269 (0.37%) 
Neutropenic colitis  1  0/229 (0.00%)  3/269 (1.12%) 
Stomatitis  1  0/229 (0.00%)  1/269 (0.37%) 
General disorders     
Disease progression  1  2/229 (0.87%)  5/269 (1.86%) 
Asthenia  1  0/229 (0.00%)  1/269 (0.37%) 
Chest pain  1  0/229 (0.00%)  1/269 (0.37%) 
Drug withdrawal syndrome  1  0/229 (0.00%)  1/269 (0.37%) 
Fatigue  1  0/229 (0.00%)  2/269 (0.74%) 
Oedema peripheral  1  0/229 (0.00%)  2/269 (0.74%) 
Pain  1  0/229 (0.00%)  1/269 (0.37%) 
Pyrexia  1  0/229 (0.00%)  1/269 (0.37%) 
Infections and infestations     
Bacterial sepsis  1  1/229 (0.44%)  0/269 (0.00%) 
Breast infection  1  1/229 (0.44%)  0/269 (0.00%) 
Liver abscess  1  1/229 (0.44%)  0/269 (0.00%) 
Sepsis syndrome  1  1/229 (0.44%)  1/269 (0.37%) 
Abscess  1  0/229 (0.00%)  1/269 (0.37%) 
Bacteraemia  1  0/229 (0.00%)  1/269 (0.37%) 
Catheter related infection  1  0/229 (0.00%)  1/269 (0.37%) 
Cellulitis  1  0/229 (0.00%)  3/269 (1.12%) 
Lobar pneumonia  1  0/229 (0.00%)  1/269 (0.37%) 
Lower respiratory tract infection  1  0/229 (0.00%)  1/269 (0.37%) 
Oesophageal candidiasis  1  0/229 (0.00%)  1/269 (0.37%) 
Pneumonia  1  0/229 (0.00%)  4/269 (1.49%) 
Sepsis  1  0/229 (0.00%)  1/269 (0.37%) 
Septic shock  1  0/229 (0.00%)  1/269 (0.37%) 
Streptococcal bacteraemia  1  0/229 (0.00%)  1/269 (0.37%) 
Urinary tract infection  1  0/229 (0.00%)  1/269 (0.37%) 
Injury, poisoning and procedural complications     
Post procedural complication  1  1/229 (0.44%)  0/269 (0.00%) 
Urostomy complication  1  1/229 (0.44%)  0/269 (0.00%) 
Femoral neck fracture  1  0/229 (0.00%)  1/269 (0.37%) 
Fibula fracture  1  0/229 (0.00%)  1/269 (0.37%) 
Hip fracture  1  0/229 (0.00%)  1/269 (0.37%) 
Humerus fracture  1  0/229 (0.00%)  1/269 (0.37%) 
Open wound  1  0/229 (0.00%)  1/269 (0.37%) 
Wound  1  0/229 (0.00%)  1/269 (0.37%) 
Investigations     
Hepatic enzyme increased  1  0/229 (0.00%)  1/269 (0.37%) 
International normalised ratio decreased  1  0/229 (0.00%)  1/269 (0.37%) 
Metabolism and nutrition disorders     
Dehydration  1  0/229 (0.00%)  1/269 (0.37%) 
Electrolyte imbalance  1  0/229 (0.00%)  2/269 (0.74%) 
Hypoglycaemia  1  0/229 (0.00%)  1/269 (0.37%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/229 (0.44%)  1/269 (0.37%) 
Musculoskeletal pain  1  0/229 (0.00%)  1/269 (0.37%) 
Myositis  1  0/229 (0.00%)  1/269 (0.37%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung cancer metastatic  1  1/229 (0.44%)  0/269 (0.00%) 
Malignant ascites  1  1/229 (0.44%)  0/269 (0.00%) 
Malignant neoplasm progression  1  5/229 (2.18%)  60/269 (22.30%) 
Myelodysplastic syndrome  1  1/229 (0.44%)  0/269 (0.00%) 
Non-small cell lung cancer  1  2/229 (0.87%)  3/269 (1.12%) 
Prostate cancer  1  1/229 (0.44%)  3/269 (1.12%) 
Bladder cancer  1  0/229 (0.00%)  1/269 (0.37%) 
Breast cancer metastatic  1  0/229 (0.00%)  1/269 (0.37%) 
Cancer pain  1  0/229 (0.00%)  4/269 (1.49%) 
Colon cancer metastatic  1  0/229 (0.00%)  1/269 (0.37%) 
Laryngeal cancer  1  0/229 (0.00%)  1/269 (0.37%) 
Lip and/or oral cavity cancer  1  0/229 (0.00%)  1/269 (0.37%) 
Lung neoplasm malignant  1  0/229 (0.00%)  1/269 (0.37%) 
Metastases to bone  1  0/229 (0.00%)  1/269 (0.37%) 
Metastases to spine  1  0/229 (0.00%)  1/269 (0.37%) 
Multiple myeloma  1  0/229 (0.00%)  1/269 (0.37%) 
Nervous system disorders     
Haemorrhage intracranial  1  1/229 (0.44%)  0/269 (0.00%) 
Cerebrovascular accident  1  0/229 (0.00%)  1/269 (0.37%) 
Renal and urinary disorders     
Hydronephrosis  1  1/229 (0.44%)  0/269 (0.00%) 
Renal failure chronic  1  1/229 (0.44%)  0/269 (0.00%) 
Real failure acute  1  0/229 (0.00%)  1/269 (0.37%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia aspiration  1  1/229 (0.44%)  1/269 (0.37%) 
Pulmonary embolism  1  1/229 (0.44%)  3/269 (1.12%) 
Respiratory distress  1  1/229 (0.44%)  1/269 (0.37%) 
Chronic obstructive pulmonary disease  1  0/229 (0.00%)  1/269 (0.37%) 
Emphysema  1  0/229 (0.00%)  1/269 (0.37%) 
Dyspnoea  1  0/229 (0.00%)  3/269 (1.12%) 
Pleural effusion  1  0/229 (0.00%)  1/269 (0.37%) 
Skin and subcutaneous tissue disorders     
Blister  1  0/229 (0.00%)  1/269 (0.37%) 
Vascular disorders     
Deep vein thrombosis  1  0/229 (0.00%)  2/269 (0.74%) 
Orthostatic hypotension  1  0/229 (0.00%)  1/269 (0.37%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Fentanyl Sublingual Spray Titration Fentanyl Sublingual Spray Maintenance
Affected / at Risk (%) Affected / at Risk (%)
Total   194/229 (84.72%)   269/269 (100.00%) 
Blood and lymphatic system disorders     
Anaemia  1  3/229 (1.31%)  17/269 (6.32%) 
Gastrointestinal disorders     
Vomiting  1  27/229 (11.79%)  43/269 (15.99%) 
Nausea  1  30/229 (13.10%)  28/269 (10.41%) 
Constipation  1  13/229 (5.68%)  28/269 (10.41%) 
Diarrhoea  1  8/229 (3.49%)  20/269 (7.43%) 
General disorders     
Oedema peripheral  1  7/229 (3.06%)  31/269 (11.52%) 
Asthenia  1  4/229 (1.75%)  26/269 (9.67%) 
Fatigue  1  7/229 (3.06%)  23/269 (8.55%) 
Application site irritation  1  17/229 (7.42%)  3/269 (1.12%) 
Pyrexia  1  11/229 (4.80%)  18/269 (6.69%) 
Metabolism and nutrition disorders     
Anorexia  1  2/229 (0.87%)  14/269 (5.20%) 
Dehydration  1  1/229 (0.44%)  14/269 (5.20%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  2/229 (0.87%)  15/269 (5.58%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant neoplasm progression  1  7/229 (3.06%)  65/269 (24.16%) 
Cancer pain  1  6/229 (2.62%)  17/269 (6.32%) 
Nervous system disorders     
Somnolence  1  23/229 (10.04%)  10/269 (3.72%) 
Dizziness  1  16/229 (6.99%)  3/269 (1.12%) 
Psychiatric disorders     
Anxiety  1  3/229 (1.31%)  16/269 (5.95%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  7/229 (3.06%)  28/269 (10.41%) 
Cough  1  0/229 (0.00%)  14/269 (5.20%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Larry Dillaha, M.D., Chief Medical Officer
Organization: Insys Therapeutics, Inc.
Phone: 602-910-2617
EMail: ldillaha@insysrx.com
Layout table for additonal information
Responsible Party: INSYS Therapeutics Inc
ClinicalTrials.gov Identifier: NCT00538863     History of Changes
Obsolete Identifiers: NCT00589004
Other Study ID Numbers: INS-06-007
First Submitted: October 1, 2007
First Posted: October 3, 2007
Results First Submitted: September 11, 2012
Results First Posted: October 11, 2013
Last Update Posted: October 11, 2013