Trial Outcomes & Findings for Baclofen-Amitriptyline Hydrochloride-Ketamine Gel in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer (NCT NCT00516503)
NCT ID: NCT00516503
Last Updated: 2017-08-24
Results Overview
The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The primary analysis was the change in sensory neuropathy subscale of the CIPN-20 from baseline to week 4. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's sensory neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
COMPLETED
PHASE3
208 participants
From baseline to 4 weeks
2017-08-24
Participant Flow
Two-hundred eight patients were enrolled to this study. Five patients cancelled prior to initiating protocol treatment and were therefore this study was analyzed using 203 remaining patients.
Participant milestones
| Measure |
Baclofen-amitriptyline Hydrochloride-ketamine
Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
|
Placebo
Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
|
|---|---|---|
|
Overall Study
STARTED
|
101
|
102
|
|
Overall Study
COMPLETED
|
101
|
102
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Baclofen-Amitriptyline Hydrochloride-Ketamine Gel in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
Baseline characteristics by cohort
| Measure |
Baclofen-amitriptyline Hydrochloride-ketamine
n=101 Participants
Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
|
Placebo
n=102 Participants
Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
|
Total
n=203 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.5 years
n=5 Participants
|
62 years
n=7 Participants
|
61 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
66 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
126 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
101 participants
n=5 Participants
|
102 participants
n=7 Participants
|
203 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From baseline to 4 weeksPopulation: There were 26 participants in the BAK arm and 27 in the placebo arm who did not provide primary endpoint data. In the BAK arm, 11 refused due to experiencing an adverse event and 15 refused for non-specified reasons. In the placebo arm, eight refused due to an adverse event, one patient died, and 18 refused for non-specified reasons.
The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The primary analysis was the change in sensory neuropathy subscale of the CIPN-20 from baseline to week 4. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's sensory neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
Outcome measures
| Measure |
Baclofen-amitriptyline Hydrochloride-ketamine
n=75 Participants
Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
|
Placebo
n=75 Participants
Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
|
|---|---|---|
|
Total Sensory Neuropathy as Measured by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life [QLQ] - Chemo-induced Peripheral Neuropathy [CIPN20]
|
61.0 (units on a scale) * week
Standard Deviation 16.22
|
60.9 (units on a scale) * week
Standard Deviation 17.9
|
SECONDARY outcome
Timeframe: From Baseline to week 4Population: There were 26 participants in the BAK arm and 27 in the placebo arm who did not provide primary endpoint data. In the BAK arm, 11 refused due to experiencing an adverse\> event and 15 refused for non-specified reasons. In the placebo arm, eight refused due to an\> adverse event, one patient died, and 18 refused for non-specified reasons.
The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the motor neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
Outcome measures
| Measure |
Baclofen-amitriptyline Hydrochloride-ketamine
n=75 Participants
Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
|
Placebo
n=75 Participants
Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
|
|---|---|---|
|
Motor Neuropathy as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4
|
69.2 (units on a scale)* week
Standard Deviation 17.15
|
70.1 (units on a scale)* week
Standard Deviation 19.48
|
SECONDARY outcome
Timeframe: Up to 4 weeksPopulation: There were 26 participants in the BAK arm and 27 in the placebo arm who did not provide primary endpoint data. In the BAK arm, 11 refused due to experiencing an adverse event and 15 refused for non-specified reasons. In the placebo arm, eight refused due to an adverse event, one patient died, and 18 refused for non-specified reasons.
The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the autonomic neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
Outcome measures
| Measure |
Baclofen-amitriptyline Hydrochloride-ketamine
n=75 Participants
Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
|
Placebo
n=75 Participants
Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
|
|---|---|---|
|
Autonomic Symptoms and Functioning as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4
|
85.0 (units on a scale)*week
Standard Deviation 15.47
|
86.8 (units on a scale)*week
Standard Deviation 15.03
|
SECONDARY outcome
Timeframe: At 4 weeksEach mood scale (0 - 100, higher is better mood) will be analyzed as an endpoint along with the total mood disturbance score.
Outcome measures
| Measure |
Baclofen-amitriptyline Hydrochloride-ketamine
n=101 Participants
Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
|
Placebo
n=102 Participants
Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
|
|---|---|---|
|
Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS)
POMS Tension-Anxiety Subscale
|
83.2 units on a scale
Standard Deviation 17.09
|
83.0 units on a scale
Standard Deviation 15.73
|
|
Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS)
POMS VA Subscale
|
31.1 units on a scale
Standard Deviation 18.42
|
33.0 units on a scale
Standard Deviation 19.61
|
|
Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS)
POMS Anger-Hostility Score
|
87.8 units on a scale
Standard Deviation 14.48
|
87.7 units on a scale
Standard Deviation 12.98
|
|
Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS)
POMS Confusion-Bewilderment
|
76.9 units on a scale
Standard Deviation 17.58
|
77.9 units on a scale
Standard Deviation 11.75
|
|
Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS)
POMS Depression-Dejection Score
|
86.4 units on a scale
Standard Deviation 16.09
|
85.8 units on a scale
Standard Deviation 15.23
|
|
Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS)
POMS Fatigue-Inertia Score
|
67.2 units on a scale
Standard Deviation 21.69
|
63.6 units on a scale
Standard Deviation 22.22
|
|
Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS)
Mean POMS Score
|
71.5 units on a scale
Standard Deviation 13.27
|
71.8 units on a scale
Standard Deviation 13.14
|
SECONDARY outcome
Timeframe: Up to 4 weeksPain severity, defined by the four items addressing worst, least, and average pain and pain right now as measured by the BPI will be analyzed identical to the primary endpoint. Additionally, total pain interference as measured by the BPI will be transformed onto a 0-100 ( higher is less pain) point scale. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.
Outcome measures
| Measure |
Baclofen-amitriptyline Hydrochloride-ketamine
n=101 Participants
Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
|
Placebo
n=102 Participants
Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
|
|---|---|---|
|
Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4
Least Pain
|
78.0 units on a scale * week
Standard Deviation 20.28
|
77.3 units on a scale * week
Standard Deviation 22.01
|
|
Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4
Average Pain
|
66.4 units on a scale * week
Standard Deviation 21.99
|
65.4 units on a scale * week
Standard Deviation 24.55
|
|
Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4
BPI Total Interference
|
76.5 units on a scale * week
Standard Deviation 20.16
|
77.3 units on a scale * week
Standard Deviation 21.16
|
|
Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4
Worst Pain
|
58.1 units on a scale * week
Standard Deviation 25.48
|
58.7 units on a scale * week
Standard Deviation 27.39
|
SECONDARY outcome
Timeframe: Up to 4 weeksThe Peripheral Neuropathy Questionnaire was used to analyze this endpoint. Patient neuropathy symptoms were scored on a 0 - 100 scale (higher score represents less symptomatic). The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.
Outcome measures
| Measure |
Baclofen-amitriptyline Hydrochloride-ketamine
n=101 Participants
Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
|
Placebo
n=102 Participants
Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
|
|---|---|---|
|
Numbness, Tingling, and Pain as Measured by the Peripheral Neuropathy Questionnaire at Baseline and Weekly for 4 Weeks
|
172.6 units on a scale * week
Standard Deviation 82.09
|
175.7 units on a scale * week
Standard Deviation 85.38
|
SECONDARY outcome
Timeframe: Up to 4 weeksPopulation: All patients that were assessed for adverse events are used in this analysis.
Frequency and severity of adverse events reported by patients in weekly diary and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report.
Outcome measures
| Measure |
Baclofen-amitriptyline Hydrochloride-ketamine
n=101 Participants
Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
|
Placebo
n=102 Participants
Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
|
|---|---|---|
|
Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0
Grade 3+ Adverse Event
|
8 Participants
|
5 Participants
|
|
Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0
Grade 4+ Adverse Event
|
1 Participants
|
1 Participants
|
Adverse Events
Baclofen-amitriptyline Hydrochloride-ketamine
Placebo
Serious adverse events
| Measure |
Baclofen-amitriptyline Hydrochloride-ketamine
n=101 participants at risk
Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
|
Placebo
n=102 participants at risk
Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
|
|---|---|---|
|
General disorders
Disease progression
|
0.00%
0/101
|
0.98%
1/102 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
0.99%
1/101 • Number of events 1
|
0.00%
0/102
|
Other adverse events
| Measure |
Baclofen-amitriptyline Hydrochloride-ketamine
n=101 participants at risk
Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
|
Placebo
n=102 participants at risk
Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
|
|---|---|---|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/101
|
0.98%
1/102 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/101
|
2.0%
2/102 • Number of events 5
|
|
Gastrointestinal disorders
Constipation
|
23.8%
24/101 • Number of events 62
|
27.5%
28/102 • Number of events 71
|
|
Gastrointestinal disorders
Diarrhea
|
0.99%
1/101 • Number of events 1
|
0.98%
1/102 • Number of events 1
|
|
Gastrointestinal disorders
Dry mouth
|
17.8%
18/101 • Number of events 55
|
22.5%
23/102 • Number of events 55
|
|
Gastrointestinal disorders
Ileal obstruction
|
0.00%
0/101
|
0.98%
1/102 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.99%
1/101 • Number of events 1
|
0.00%
0/102
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/101
|
2.0%
2/102 • Number of events 4
|
|
Gastrointestinal disorders
Stomach pain
|
0.00%
0/101
|
0.00%
0/102
|
|
Gastrointestinal disorders
Vomiting
|
0.99%
1/101 • Number of events 1
|
0.00%
0/102
|
|
General disorders
Edema limbs
|
0.99%
1/101 • Number of events 1
|
0.98%
1/102 • Number of events 1
|
|
General disorders
Fatigue
|
0.99%
1/101 • Number of events 1
|
0.98%
1/102 • Number of events 1
|
|
General disorders
Pain
|
0.00%
0/101
|
0.00%
0/102
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/101
|
0.98%
1/102 • Number of events 1
|
|
Infections and infestations
Bladder infection
|
0.00%
0/101
|
0.00%
0/102
|
|
Infections and infestations
Skin infection
|
0.99%
1/101 • Number of events 2
|
0.00%
0/102
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/101
|
0.00%
0/102
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/101
|
0.98%
1/102 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/101
|
0.98%
1/102 • Number of events 1
|
|
Investigations
Platelet count decreased
|
0.00%
0/101
|
0.98%
1/102 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/101
|
0.00%
0/102
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
0.00%
0/101
|
0.00%
0/102
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
0.99%
1/101 • Number of events 1
|
0.00%
0/102
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.99%
1/101 • Number of events 1
|
0.00%
0/102
|
|
Nervous system disorders
Ataxia
|
0.00%
0/101
|
0.98%
1/102 • Number of events 1
|
|
Nervous system disorders
Depressed level of consciousness
|
2.0%
2/101 • Number of events 2
|
2.0%
2/102 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
0.00%
0/101
|
0.00%
0/102
|
|
Nervous system disorders
Neuralgia
|
0.99%
1/101 • Number of events 1
|
0.00%
0/102
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/101
|
2.0%
2/102 • Number of events 2
|
|
Nervous system disorders
Syncope vasovagal
|
0.00%
0/101
|
0.00%
0/102
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/101
|
0.00%
0/102
|
|
Psychiatric disorders
Confusion
|
5.0%
5/101 • Number of events 5
|
3.9%
4/102 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.99%
1/101 • Number of events 1
|
0.00%
0/102
|
|
Skin and subcutaneous tissue disorders
Hand-and-foot syndrome
|
15.8%
16/101 • Number of events 26
|
11.8%
12/102 • Number of events 25
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/101
|
0.00%
0/102
|
|
Vascular disorders
Thrombosis
|
0.00%
0/101
|
0.98%
1/102 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place