Fentanyl Sublingual Spray in Treating Patients With Breakthrough Cancer Pain
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 Names:
Drug: Placebo
Matching placebo to fentanyl sublingual spray.
|
Outcome Measures
Primary Outcome Measures
- Summed Pain Intensity Differences (SPID) at 30 Minutes After Dosing (SPID30) [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 Outcome Measures
- Summed Pain Intensity Differences (SPID) at 5, 10, 15, 45, and 60 Minutes After Dosing [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.
- Total Pain Relief (TOTPAR) at 5, 10, 15, 30, 45, and 60 Minutes After Dosing [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.
- Global Evaluation of the Study Medication at 30 and 60 Minutes After Dosing [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.
Eligibility Criteria
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 > 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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | InSys Therapeutics, Incorporated | Chandler | Arizona | United States | 85224 |
Sponsors and Collaborators
- INSYS Therapeutics Inc
- National Cancer Institute (NCI)
Investigators
- Study Chair: Larry Dillaha, MD, INSYS Therapeutics Inc
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- INS-05-001
- CDR0000581128
- NCT00589342
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | As there are dozens, if not hundreds, of cross-over sequences during the double-blind period of this study, instead of reporting participant flow for each of the cross-over sequences, participant flow is reported separately for the fentanyl and placebo groups. |
| Arm/Group Title | Fentanyl Sublingual Spray - Titration | Fentanyl Sublingual Spray - Double-blind | Placebo - Double-blind |
|---|---|---|---|
| Arm/Group Description | 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. | Participants received fentanyl sublingual spray 7 times randomly (out of 10 treatments total) 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. | Participants received placebo 3 times randomly (out of 10 treatments total) 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. |
| Period Title: Titration Period | |||
| STARTED | 130 | 0 | 0 |
| COMPLETED | 98 | 0 | 0 |
| NOT COMPLETED | 32 | 0 | 0 |
| Period Title: Titration Period | |||
| STARTED | 0 | 98 | 0 |
| COMPLETED | 0 | 95 | 0 |
| NOT COMPLETED | 0 | 3 | 0 |
| Period Title: Titration Period | |||
| STARTED | 0 | 0 | 98 |
| COMPLETED | 0 | 0 | 95 |
| NOT COMPLETED | 0 | 0 | 3 |
Baseline Characteristics
| Arm/Group Title | Fentanyl Sublingual Spray |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 130 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
55.6
(12.2)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
69
53.1%
|
| Male |
61
46.9%
|
Outcome Measures
| Title | Summed Pain Intensity Differences (SPID) at 30 Minutes After Dosing (SPID30) |
|---|---|
| Description | 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. |
| Time Frame | Baseline (time 0, beginning of each pain episode) through 30 minutes after dosing for each pain episode |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: All participants in the double-blind treatment period who received at least 1 dose of study medication and had at least 1 pain measurement. 4 of the 96 participants in the ITT population were excluded from analysis because they did not have at least 1 dose of study medication and 1 dose of placebo. |
| Arm/Group Title | Fentanyl Sublingual Spray | Placebo |
|---|---|---|
| Arm/Group Description | Participants received fentanyl sublingual spray 7 times randomly (out of 10 treatments total) 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. | Participants received placebo 3 times randomly (out of 10 treatments total) 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. |
| Measure Participants | 92 | 92 |
| Mean (Standard Deviation) [Units on a scale] |
640.3
(458.8)
|
399.6
(391.2)
|
| Title | Summed Pain Intensity Differences (SPID) at 5, 10, 15, 45, and 60 Minutes After Dosing |
|---|---|
| Description | 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. |
| Time Frame | Baseline (time 0, beginning of each pain episode) through 60 minutes after dosing for each pain episode |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: All participants in the double-blind treatment period who received at least 1 dose of study medication and had at least 1 pain measurement. 4 of the 96 participants in the ITT population were excluded from analysis because they did not have at least 1 dose of study medication and 1 dose of placebo. |
| Arm/Group Title | Fentanyl Sublingual Spray | Placebo |
|---|---|---|
| Arm/Group Description | Participants received fentanyl sublingual spray 7 times randomly (out of 10 treatments total) 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. | Participants received placebo 3 times randomly (out of 10 treatments total) 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. |
| Measure Participants | 92 | 92 |
| SPID5 |
40.3
(57.7)
|
32.0
(52.1)
|
| SPID10 |
115.0
(130.7)
|
81.1
(108.0)
|
| SPID15 |
220.6
(209.7)
|
150.3
(172.5)
|
| SPID45 |
1122.0
(731.9)
|
667.0
(614.5)
|
| SPID60 |
1649.0
(1016.2)
|
965.7
(862.1)
|
| Title | Total Pain Relief (TOTPAR) at 5, 10, 15, 30, 45, and 60 Minutes After Dosing |
|---|---|
| Description | 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. |
| Time Frame | 5 through 60 minutes after dosing for each pain episode |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: All participants in the double-blind treatment period who received at least 1 dose of study medication and had at least 1 pain measurement. 4 of the 96 participants in the ITT population were excluded from analysis because they did not have at least 1 dose of study medication and 1 dose of placebo. |
| Arm/Group Title | Fentanyl Sublingual Spray | Placebo |
|---|---|---|
| Arm/Group Description | Participants received fentanyl sublingual spray 7 times randomly (out of 10 treatments total) 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. | Participants received placebo 3 times randomly (out of 10 treatments total) 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. |
| Measure Participants | 92 | 92 |
| TOTPAR5 |
8.6
(3.5)
|
7.6
(3.3)
|
| TOTPAR10 |
19.7
(7.0)
|
16.7
(6.5)
|
| TOTPAR15 |
32.9
(10.3)
|
27.1
(10.0)
|
| TOTPAR30 |
78.3
(20.4)
|
61.0
(20.8)
|
| TOTPAR45 |
126.3
(30.9)
|
95.5
(32.0)
|
| TOTPAR60 |
176.4
(41.5)
|
131.2
(43.6)
|
| Title | Global Evaluation of the Study Medication at 30 and 60 Minutes After Dosing |
|---|---|
| Description | 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. |
| Time Frame | 30 through 60 minutes after dosing for each pain episode |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population: All participants in the double-blind treatment period who received at least 1 dose of study medication and had at least 1 pain measurement. 4 of the 96 participants in the ITT population were excluded from analysis because they did not have at least 1 dose of study medication and 1 dose of placebo. |
| Arm/Group Title | Fentanyl Sublingual Spray | Placebo |
|---|---|---|
| Arm/Group Description | Participants received fentanyl sublingual spray 7 times randomly (out of 10 treatments total) 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. | Participants received placebo 3 times randomly (out of 10 treatments total) 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. |
| Measure Participants | 92 | 92 |
| 30 minutes |
2.8
(0.8)
|
2.0
(0.8)
|
| 60 minutes |
3.1
(0.8)
|
2.2
(0.8)
|
Adverse Events
| Time Frame | All adverse events were followed to resolution, an outcome was reached, stabilization, or the event was otherwise explained regardless of whether the subject was still participating in the study. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population: All enrolled subjects who took at least 1 dose of fentanyl sublingual spray. As subjects may have taken both treatments on the same day and adverse events were only collected once each day, it is not possible to report adverse events separately for the 2 treatments. | |||
| Arm/Group Title | Fentanyl Sublingual Spray - Titration | Fentanyl Sublingual Spray - Double-blind | ||
| Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
| Fentanyl Sublingual Spray - Titration | Fentanyl Sublingual Spray - Double-blind | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Fentanyl Sublingual Spray - Titration | Fentanyl Sublingual Spray - Double-blind | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/130 (5.4%) | 6/98 (6.1%) | ||
| Blood and lymphatic system disorders | ||||
| Leukopenia | 1/130 (0.8%) | 0/98 (0%) | ||
| Cardiac disorders | ||||
| Tachycardia | 0/130 (0%) | 1/98 (1%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/130 (0.8%) | 1/98 (1%) | ||
| Nausea | 1/130 (0.8%) | 1/98 (1%) | ||
| Vomiting | 1/130 (0.8%) | 1/98 (1%) | ||
| Infections and infestations | ||||
| Cellulitis | 1/130 (0.8%) | 1/98 (1%) | ||
| Gastroenteritis Viral | 0/130 (0%) | 1/98 (1%) | ||
| Metabolism and nutrition disorders | ||||
| Hyponatraemia | 1/130 (0.8%) | 0/98 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Fistula | 1/130 (0.8%) | 0/98 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Lung cancer metastatic | 1/130 (0.8%) | 0/98 (0%) | ||
| Malignant neoplasm progression | 1/130 (0.8%) | 1/98 (1%) | ||
| Metastases to bone | 1/130 (0.8%) | 0/98 (0%) | ||
| Spinal cord neoplasm | 1/130 (0.8%) | 0/98 (0%) | ||
| Nervous system disorders | ||||
| Paraplegia | 0/130 (0%) | 1/98 (1%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Fentanyl Sublingual Spray - Titration | Fentanyl Sublingual Spray - Double-blind | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 78/130 (60%) | 47/98 (48%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/130 (0.8%) | 2/98 (2%) | ||
| Leukopenia | 1/130 (0.8%) | 0/98 (0%) | ||
| Lymphadenopathy | 1/130 (0.8%) | 0/98 (0%) | ||
| Pancytopenia | 0/130 (0%) | 1/98 (1%) | ||
| Cardiac disorders | ||||
| Tachycardia | 1/130 (0.8%) | 1/98 (1%) | ||
| Right ventricular hypertrophy | 0/130 (0%) | 1/98 (1%) | ||
| Sinus tachycardia | 0/130 (0%) | 1/98 (1%) | ||
| Ear and labyrinth disorders | ||||
| Ear pain | 1/130 (0.8%) | 0/98 (0%) | ||
| Vertigo | 1/130 (0.8%) | 0/98 (0%) | ||
| Eye disorders | ||||
| Dry eye | 1/130 (0.8%) | 0/98 (0%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 17/130 (13.1%) | 7/98 (7.1%) | ||
| Vomiting | 10/130 (7.7%) | 4/98 (4.1%) | ||
| Diarrhoea | 7/130 (5.4%) | 3/98 (3.1%) | ||
| Constipation | 5/130 (3.8%) | 0/98 (0%) | ||
| Stomatitis | 5/130 (3.8%) | 1/98 (1%) | ||
| Dry mouth | 2/130 (1.5%) | 2/98 (2%) | ||
| Abdominal discomfort | 1/130 (0.8%) | 0/98 (0%) | ||
| Abdominal distension | 1/130 (0.8%) | 0/98 (0%) | ||
| Abdominal pain | 1/130 (0.8%) | 1/98 (1%) | ||
| Abdominal pain upper | 1/130 (0.8%) | 0/98 (0%) | ||
| Dysphagia | 1/130 (0.8%) | 0/98 (0%) | ||
| Flatulence | 1/130 (0.8%) | 1/98 (1%) | ||
| Gastric ulcer | 1/130 (0.8%) | 0/98 (0%) | ||
| Gastrointestinal motility disorder | 1/130 (0.8%) | 0/98 (0%) | ||
| Gingival hyperplasia | 1/130 (0.8%) | 0/98 (0%) | ||
| Glossitis | 1/130 (0.8%) | 0/98 (0%) | ||
| Hyperchlorhydria | 1/130 (0.8%) | 0/98 (0%) | ||
| Hypoaesthesia oral | 1/130 (0.8%) | 0/98 (0%) | ||
| Odynophagia | 1/130 (0.8%) | 0/98 (0%) | ||
| Oral pain | 1/130 (0.8%) | 0/98 (0%) | ||
| Retching | 1/130 (0.8%) | 1/98 (1%) | ||
| Tongue ulceration | 1/130 (0.8%) | 0/98 (0%) | ||
| Abdominal pain lower | 0/130 (0%) | 2/98 (2%) | ||
| Aphthous stomatitis | 0/130 (0%) | 1/98 (1%) | ||
| Ascites | 0/130 (0%) | 1/98 (1%) | ||
| Colitis | 0/130 (0%) | 1/98 (1%) | ||
| Lip disorder | 0/130 (0%) | 1/98 (1%) | ||
| Oral mucosal discolouration | 0/130 (0%) | 1/98 (1%) | ||
| Salivary gland enlargement | 0/130 (0%) | 1/98 (1%) | ||
| General disorders | ||||
| Pyrexia | 8/130 (6.2%) | 1/98 (1%) | ||
| Oedema peripheral | 7/130 (5.4%) | 5/98 (5.1%) | ||
| Asthenia | 4/130 (3.1%) | 2/98 (2%) | ||
| Fatigue | 4/130 (3.1%) | 2/98 (2%) | ||
| Application site irritation | 3/130 (2.3%) | 0/98 (0%) | ||
| Adverse drug reaction | 1/130 (0.8%) | 0/98 (0%) | ||
| Catheter related complication | 1/130 (0.8%) | 0/98 (0%) | ||
| Catheter site erythema | 1/130 (0.8%) | 0/98 (0%) | ||
| Chest discomfort | 1/130 (0.8%) | 1/98 (1%) | ||
| Feeling abnormal | 1/130 (0.8%) | 0/98 (0%) | ||
| Localised oedema | 1/130 (0.8%) | 0/98 (0%) | ||
| Mucosal inflammation | 1/130 (0.8%) | 0/98 (0%) | ||
| Pain | 1/130 (0.8%) | 1/98 (1%) | ||
| Thirst | 1/130 (0.8%) | 0/98 (0%) | ||
| Chills | 0/130 (0%) | 1/98 (1%) | ||
| Malaise | 0/130 (0%) | 1/98 (1%) | ||
| Mass | 0/130 (0%) | 1/98 (1%) | ||
| Hepatobiliary disorders | ||||
| Jaundice cholestatic | 1/130 (0.8%) | 0/98 (0%) | ||
| Infections and infestations | ||||
| Urinary tract infection | 5/130 (3.8%) | 3/98 (3.1%) | ||
| Cellulitis | 2/130 (1.5%) | 1/98 (1%) | ||
| Gastroenteritis viral | 1/130 (0.8%) | 1/98 (1%) | ||
| Oral herpes | 1/130 (0.8%) | 0/98 (0%) | ||
| Pneumonia | 1/130 (0.8%) | 1/98 (1%) | ||
| Pyelonephritis | 1/130 (0.8%) | 0/98 (0%) | ||
| Upper respiratory tract infection | 1/130 (0.8%) | 0/98 (0%) | ||
| Viral upper respiratory tract infection | 1/130 (0.8%) | 0/98 (0%) | ||
| Candidiasis | 0/130 (0%) | 1/98 (1%) | ||
| Extradural abscess | 0/130 (0%) | 1/98 (1%) | ||
| Fungal infection | 0/130 (0%) | 1/98 (1%) | ||
| Nasopharyngitis | 0/130 (0%) | 1/98 (1%) | ||
| Oral viral infection | 0/130 (0%) | 1/98 (1%) | ||
| Pharyngitis | 0/130 (0%) | 1/98 (1%) | ||
| Sinusitis | 0/130 (0%) | 1/98 (1%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 2/130 (1.5%) | 0/98 (0%) | ||
| Contusion | 1/130 (0.8%) | 0/98 (0%) | ||
| Device breakage | 1/130 (0.8%) | 0/98 (0%) | ||
| Excoriation | 1/130 (0.8%) | 0/98 (0%) | ||
| Radiation injury | 1/130 (0.8%) | 1/98 (1%) | ||
| Radiation mucositis | 0/130 (0%) | 1/98 (1%) | ||
| Investigations | ||||
| Blood bilirubin increased | 1/130 (0.8%) | 0/98 (0%) | ||
| Blood creatinine increased | 1/130 (0.8%) | 0/98 (0%) | ||
| Blood glucose increased | 1/130 (0.8%) | 0/98 (0%) | ||
| Blood potassium decreased | 1/130 (0.8%) | 1/98 (1%) | ||
| Blood urea increased | 1/130 (0.8%) | 0/98 (0%) | ||
| International normalised ratio increased | 1/130 (0.8%) | 0/98 (0%) | ||
| Prothrombin time prolonged | 1/130 (0.8%) | 0/98 (0%) | ||
| Breath sounds abnormal | 0/130 (0%) | 1/98 (1%) | ||
| Electrocardiogram Qrs complex abnormal | 0/130 (0%) | 1/98 (1%) | ||
| Weight decreased | 0/130 (0%) | 1/98 (1%) | ||
| Weight increased | 0/130 (0%) | 1/98 (1%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 2/130 (1.5%) | 0/98 (0%) | ||
| Dehydration | 2/130 (1.5%) | 0/98 (0%) | ||
| Decreased appetite | 1/130 (0.8%) | 0/98 (0%) | ||
| Hypokalaemia | 1/130 (0.8%) | 0/98 (0%) | ||
| Hyponatraemia | 1/130 (0.8%) | 0/98 (0%) | ||
| Increased appetite | 1/130 (0.8%) | 0/98 (0%) | ||
| Malnutrition | 1/130 (0.8%) | 0/98 (0%) | ||
| Glucose tolerance impaired | 0/130 (0%) | 1/98 (1%) | ||
| Hypomagnesaemia | 0/130 (0%) | 1/98 (1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 3/130 (2.3%) | 1/98 (1%) | ||
| Arthralgia | 2/130 (1.5%) | 1/98 (1%) | ||
| Fistula | 2/130 (1.5%) | 0/98 (0%) | ||
| Joint swelling | 2/130 (1.5%) | 0/98 (0%) | ||
| Limb discomfort | 1/130 (0.8%) | 0/98 (0%) | ||
| Mobility decreased | 1/130 (0.8%) | 0/98 (0%) | ||
| Muscle spasms | 1/130 (0.8%) | 0/98 (0%) | ||
| Pain in extremity | 0/130 (0%) | 2/98 (2%) | ||
| Bone pain | 0/130 (0%) | 1/98 (1%) | ||
| Flank pain | 0/130 (0%) | 1/98 (1%) | ||
| Muscular weakness | 0/130 (0%) | 1/98 (1%) | ||
| Myalgia | 0/130 (0%) | 1/98 (1%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Malignant neoplasm progression | 3/130 (2.3%) | 1/98 (1%) | ||
| Cancer pain | 1/130 (0.8%) | 0/98 (0%) | ||
| Lung cancer metastatic | 1/130 (0.8%) | 0/98 (0%) | ||
| Metastases to bone | 1/130 (0.8%) | 0/98 (0%) | ||
| Spinal cord neoplasm | 1/130 (0.8%) | 0/98 (0%) | ||
| Neoplasm | 0/130 (0%) | 1/98 (1%) | ||
| Polycythaemia vera | 0/130 (0%) | 1/98 (1%) | ||
| Nervous system disorders | ||||
| Somnolence | 11/130 (8.5%) | 2/98 (2%) | ||
| Dizziness | 10/130 (7.7%) | 2/98 (2%) | ||
| Headache | 5/130 (3.8%) | 3/98 (3.1%) | ||
| Sedation | 4/130 (3.1%) | 0/98 (0%) | ||
| Dysgeusia | 3/130 (2.3%) | 0/98 (0%) | ||
| Lethargy | 2/130 (1.5%) | 0/98 (0%) | ||
| Areflexia | 1/130 (0.8%) | 0/98 (0%) | ||
| Balance disorder | 1/130 (0.8%) | 0/98 (0%) | ||
| Burning sensation | 1/130 (0.8%) | 0/98 (0%) | ||
| Disturbance In attention | 1/130 (0.8%) | 0/98 (0%) | ||
| Dyskinesia | 1/130 (0.8%) | 0/98 (0%) | ||
| Facial palsy | 1/130 (0.8%) | 0/98 (0%) | ||
| Hyperreflexia | 1/130 (0.8%) | 0/98 (0%) | ||
| Hypoaesthesia | 1/130 (0.8%) | 0/98 (0%) | ||
| Paraesthesia | 1/130 (0.8%) | 0/98 (0%) | ||
| Neuralgia | 0/130 (0%) | 1/98 (1%) | ||
| Paraplegia | 0/130 (0%) | 1/98 (1%) | ||
| Spinal cord disorder | 0/130 (0%) | 1/98 (1%) | ||
| Psychiatric disorders | ||||
| Confusional state | 4/130 (3.1%) | 0/98 (0%) | ||
| Insomnia | 4/130 (3.1%) | 1/98 (1%) | ||
| Agitation | 2/130 (1.5%) | 0/98 (0%) | ||
| Hallucination | 2/130 (1.5%) | 0/98 (0%) | ||
| Anxiety | 1/130 (0.8%) | 1/98 (1%) | ||
| Depression | 1/130 (0.8%) | 0/98 (0%) | ||
| Disorientation | 1/130 (0.8%) | 0/98 (0%) | ||
| Mood swings | 1/130 (0.8%) | 0/98 (0%) | ||
| Paranoia | 1/130 (0.8%) | 0/98 (0%) | ||
| Restlessness | 1/130 (0.8%) | 0/98 (0%) | ||
| Euphoric mood | 0/130 (0%) | 1/98 (1%) | ||
| Nervousness | 0/130 (0%) | 1/98 (1%) | ||
| Renal and urinary disorders | ||||
| Urinary retention | 3/130 (2.3%) | 0/98 (0%) | ||
| Bladder distension | 1/130 (0.8%) | 0/98 (0%) | ||
| Bladder spasm | 1/130 (0.8%) | 0/98 (0%) | ||
| Haematuria | 1/130 (0.8%) | 0/98 (0%) | ||
| Micturition urgency | 1/130 (0.8%) | 0/98 (0%) | ||
| Renal impairment | 0/130 (0%) | 1/98 (1%) | ||
| Urinary incontinence | 0/130 (0%) | 1/98 (1%) | ||
| Reproductive system and breast disorders | ||||
| Amenorrhoea | 1/69 (1.4%) | 0/98 (0%) | ||
| Epididymitis | 1/61 (1.6%) | 0/98 (0%) | ||
| Vaginal haemorrhage | 1/69 (1.4%) | 0/98 (0%) | ||
| Vaginal ulceration | 0/130 (0%) | 1/98 (1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 4/130 (3.1%) | 0/98 (0%) | ||
| Cough | 3/130 (2.3%) | 3/98 (3.1%) | ||
| Increased bronchial secretion | 3/130 (2.3%) | 0/98 (0%) | ||
| Dysphonia | 1/130 (0.8%) | 0/98 (0%) | ||
| Epistaxis | 1/130 (0.8%) | 1/98 (1%) | ||
| Hiccups | 1/130 (0.8%) | 0/98 (0%) | ||
| Increased upper airway secretion | 1/130 (0.8%) | 0/98 (0%) | ||
| Pharyngolaryngeal pain | 1/130 (0.8%) | 0/98 (0%) | ||
| Pulmonary congestion | 1/130 (0.8%) | 0/98 (0%) | ||
| Respiratory tract congestion | 1/130 (0.8%) | 0/98 (0%) | ||
| Throat irritation | 1/130 (0.8%) | 0/98 (0%) | ||
| Wheezing | 1/130 (0.8%) | 1/98 (1%) | ||
| Pharyngeal inflammation | 0/130 (0%) | 1/98 (1%) | ||
| Productive cough | 0/130 (0%) | 1/98 (1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Hyperhidrosis | 2/130 (1.5%) | 5/98 (5.1%) | ||
| Alopecia | 1/130 (0.8%) | 0/98 (0%) | ||
| Blister | 1/130 (0.8%) | 0/98 (0%) | ||
| Erythema | 1/130 (0.8%) | 0/98 (0%) | ||
| Pruritus | 1/130 (0.8%) | 0/98 (0%) | ||
| Rash | 1/130 (0.8%) | 0/98 (0%) | ||
| Rash erythematous | 1/130 (0.8%) | 0/98 (0%) | ||
| Rash maculo-papular | 1/130 (0.8%) | 0/98 (0%) | ||
| Skin lesion | 1/130 (0.8%) | 0/98 (0%) | ||
| Urticaria | 1/130 (0.8%) | 0/98 (0%) | ||
| Dermatitis contact | 0/130 (0%) | 1/98 (1%) | ||
| Ecchymosis | 0/130 (0%) | 1/98 (1%) | ||
| Rash macular | 0/130 (0%) | 1/98 (1%) | ||
| Stasis dermatitis | 0/130 (0%) | 1/98 (1%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 1/130 (0.8%) | 1/98 (1%) | ||
| Hypertension | 1/130 (0.8%) | 2/98 (2%) | ||
| Hypotension | 1/130 (0.8%) | 0/98 (0%) | ||
| Venous stasis | 1/130 (0.8%) | 0/98 (0%) | ||
| Flushing | 0/130 (0%) | 2/98 (2%) | ||
Limitations/Caveats
More Information
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
| Name/Title | Larry Dillaha, M.D., Chief Medical Officer |
|---|---|
| Organization | Insys Therapeutics, Inc. |
| Phone | 602 910-2617 |
| ldillaha@insysrx.com |
- INS-05-001
- CDR0000581128
- NCT00589342