Trial Outcomes & Findings for Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients (NCT NCT00471445)
NCT ID: NCT00471445
Last Updated: 2015-11-09
Results Overview
Cancer survivors who completed chemotherapy at least 1 month prior and had Chemotherapy Induced Peripheral Neuropathy (CIPN) (greater than or equal to 4 out of 10) were enrolled. CIPN was assessed using average scores from a 7-day daily diary that asks patients to rate the average "pain, numbness, or tingling in their hands and feet over the past 24 hours" on an 11-point numeric rating scale at baseline and 6 weeks post intervention. CIPN ranges from 0 (no pain) to 10 (worst possible pain).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
462 participants
Primary outcome timeframe
Week 6 - Baseline
Results posted on
2015-11-09
Participant Flow
Participant milestones
| Measure |
Amitriptyline and Ketamine Hydrochloride Topical Analgesic cr
Patients apply amitriptyline and ketamine hydrochloride topical analgesic cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
ketamine/amitriptyline NP-H cream: Applied topically
|
Placebo Cream
Patients apply a placebo cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
placebo: Applied topically
|
|---|---|---|
|
Overall Study
STARTED
|
229
|
233
|
|
Overall Study
COMPLETED
|
227
|
231
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
| Measure |
Amitriptyline and Ketamine Hydrochloride Topical Analgesic cr
Patients apply amitriptyline and ketamine hydrochloride topical analgesic cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
ketamine/amitriptyline NP-H cream: Applied topically
|
Placebo Cream
Patients apply a placebo cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
placebo: Applied topically
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Ineligible
|
1
|
0
|
|
Overall Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
Baseline characteristics by cohort
| Measure |
Amitriptyline and Ketamine Hydrochloride Topical Analgesic cr
n=227 Participants
Patients apply amitriptyline and ketamine hydrochloride topical analgesic cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
ketamine/amitriptyline NP-H cream: Applied topically
|
Placebo Cream
n=231 Participants
Patients apply a placebo cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
placebo: Applied topically
|
Total
n=458 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.7 years
STANDARD_DEVIATION 10.5 • n=5 Participants
|
60.6 years
STANDARD_DEVIATION 10.0 • n=7 Participants
|
60.7 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
156 Participants
n=5 Participants
|
171 Participants
n=7 Participants
|
327 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
71 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
131 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
220 Participants
n=5 Participants
|
224 Participants
n=7 Participants
|
444 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
20 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
199 Participants
n=5 Participants
|
206 Participants
n=7 Participants
|
405 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
227 participants
n=5 Participants
|
231 participants
n=7 Participants
|
458 participants
n=5 Participants
|
|
Education
Completed graduate training
|
28 participants
n=5 Participants
|
19 participants
n=7 Participants
|
47 participants
n=5 Participants
|
|
Education
Standard college or university (4 years)
|
53 participants
n=5 Participants
|
55 participants
n=7 Participants
|
108 participants
n=5 Participants
|
|
Education
Partial college training (<4 years)
|
76 participants
n=5 Participants
|
80 participants
n=7 Participants
|
156 participants
n=5 Participants
|
|
Education
High school graduate
|
63 participants
n=5 Participants
|
65 participants
n=7 Participants
|
128 participants
n=5 Participants
|
|
Education
Not high school educated
|
7 participants
n=5 Participants
|
12 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Marital status
Married
|
165 participants
n=5 Participants
|
160 participants
n=7 Participants
|
325 participants
n=5 Participants
|
|
Marital status
Divorced
|
20 participants
n=5 Participants
|
25 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Marital status
Separated
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Marital status
Single
|
23 participants
n=5 Participants
|
21 participants
n=7 Participants
|
44 participants
n=5 Participants
|
|
Marital status
Widowed
|
17 participants
n=5 Participants
|
22 participants
n=7 Participants
|
39 participants
n=5 Participants
|
|
Previous treatment
Previous surgery
|
198 participants
n=5 Participants
|
195 participants
n=7 Participants
|
393 participants
n=5 Participants
|
|
Previous treatment
Previous chemotherapy
|
227 participants
n=5 Participants
|
231 participants
n=7 Participants
|
458 participants
n=5 Participants
|
|
Previous treatment
Previous radiation therapy
|
114 participants
n=5 Participants
|
109 participants
n=7 Participants
|
223 participants
n=5 Participants
|
|
Site
Hematologic
|
24 participants
n=5 Participants
|
18 participants
n=7 Participants
|
42 participants
n=5 Participants
|
|
Site
Head and neck
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Site
Lung
|
12 participants
n=5 Participants
|
23 participants
n=7 Participants
|
35 participants
n=5 Participants
|
|
Site
GI
|
55 participants
n=5 Participants
|
69 participants
n=7 Participants
|
124 participants
n=5 Participants
|
|
Site
Genitourinary tract
|
15 participants
n=5 Participants
|
9 participants
n=7 Participants
|
24 participants
n=5 Participants
|
|
Site
Gynecologic
|
15 participants
n=5 Participants
|
16 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Site
Breast
|
96 participants
n=5 Participants
|
88 participants
n=7 Participants
|
184 participants
n=5 Participants
|
|
Site
Skin
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Site
Melanoma
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Site
Soft tissue sarcoma
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Site
Bone and cartilaginous
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Site
Cardiac
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Site
Other
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Regimen
Taxanes
|
126 participants
n=5 Participants
|
120 participants
n=7 Participants
|
246 participants
n=5 Participants
|
|
Regimen
Non-Taxane
|
101 participants
n=5 Participants
|
111 participants
n=7 Participants
|
212 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 6 - BaselineCancer survivors who completed chemotherapy at least 1 month prior and had Chemotherapy Induced Peripheral Neuropathy (CIPN) (greater than or equal to 4 out of 10) were enrolled. CIPN was assessed using average scores from a 7-day daily diary that asks patients to rate the average "pain, numbness, or tingling in their hands and feet over the past 24 hours" on an 11-point numeric rating scale at baseline and 6 weeks post intervention. CIPN ranges from 0 (no pain) to 10 (worst possible pain).
Outcome measures
| Measure |
Ketamine/Amitriptyline NP-H Cream
n=227 Participants
Patients apply amitriptyline and ketamine hydrochloride topical analgesic cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
ketamine/amitriptyline NP-H cream: Applied topically
|
Placebo Cream
n=231 Participants
Patients apply a placebo cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
placebo: Applied topically
|
|---|---|---|
|
Change in Average Daily Peripheral Neuropathy Intensity Score From Baseline to Week 6 in Patients Treated With Amitriptyline and Ketamine Hydrochloride vs Placebo
Baseline
|
6.55 units on a scale
Interval 6.35 to 6.76
|
6.47 units on a scale
Interval 6.28 to 6.66
|
|
Change in Average Daily Peripheral Neuropathy Intensity Score From Baseline to Week 6 in Patients Treated With Amitriptyline and Ketamine Hydrochloride vs Placebo
Week 6
|
4.93 units on a scale
Interval 4.59 to 5.27
|
5.19 units on a scale
Interval 4.89 to 5.49
|
Adverse Events
Amitriptyline and Ketamine Hydrochloride Topical Analgesic cr
Serious events: 4 serious events
Other events: 147 other events
Deaths: 0 deaths
Placebo Cream
Serious events: 4 serious events
Other events: 158 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Amitriptyline and Ketamine Hydrochloride Topical Analgesic cr
n=227 participants at risk
Patients apply amitriptyline and ketamine hydrochloride topical analgesic cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
ketamine/amitriptyline NP-H cream: Applied topically
|
Placebo Cream
n=231 participants at risk
Patients apply a placebo cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
placebo: Applied topically
|
|---|---|---|
|
Immune system disorders
Allergic Rhinitis
|
0.00%
0/227
|
0.43%
1/231
|
|
Cardiac disorders
Arrythmia recurrence - pacemaker placed
|
0.00%
0/227
|
0.43%
1/231
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/227
|
0.43%
1/231
|
|
Nervous system disorders
Sensory Neuropathy
|
0.44%
1/227
|
0.00%
0/231
|
|
Musculoskeletal and connective tissue disorders
Pain in ribs
|
0.44%
1/227
|
0.00%
0/231
|
|
Skin and subcutaneous tissue disorders
Skin Rash
|
0.44%
1/227
|
0.00%
0/231
|
|
Cardiac disorders
Open Heart Surgery
|
0.44%
1/227
|
0.00%
0/231
|
|
Renal and urinary disorders
Vaginal Bleeding
|
0.00%
0/227
|
0.43%
1/231
|
Other adverse events
| Measure |
Amitriptyline and Ketamine Hydrochloride Topical Analgesic cr
n=227 participants at risk
Patients apply amitriptyline and ketamine hydrochloride topical analgesic cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
ketamine/amitriptyline NP-H cream: Applied topically
|
Placebo Cream
n=231 participants at risk
Patients apply a placebo cream twice daily to areas of pain, numbness, or tingling in the hands and/or feet.
placebo: Applied topically
|
|---|---|---|
|
Metabolism and nutrition disorders
Anorexia
|
1.3%
3/227
|
0.43%
1/231
|
|
Metabolism and nutrition disorders
Chills
|
0.00%
0/227
|
0.87%
2/231
|
|
Metabolism and nutrition disorders
Dehydration
|
0.88%
2/227
|
0.43%
1/231
|
|
Ear and labyrinth disorders
Dizziness
|
0.88%
2/227
|
1.3%
3/231
|
|
Metabolism and nutrition disorders
Drymouth
|
0.44%
1/227
|
0.00%
0/231
|
|
General disorders
Fatigue
|
3.5%
8/227
|
4.8%
11/231
|
|
Infections and infestations
Fever
|
1.3%
3/227
|
1.7%
4/231
|
|
Ear and labyrinth disorders
Tinnitus
|
0.88%
2/227
|
0.43%
1/231
|
|
General disorders
Hotflashes
|
0.44%
1/227
|
0.00%
0/231
|
|
General disorders
Insomnia
|
2.2%
5/227
|
3.0%
7/231
|
|
Hepatobiliary disorders
Liver enzymes
|
0.88%
2/227
|
1.7%
4/231
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/227
|
0.43%
1/231
|
|
Infections and infestations
Infection - Herpes Zoster
|
0.88%
2/227
|
0.43%
1/231
|
|
Skin and subcutaneous tissue disorders
Edema - Upper Extremities
|
0.88%
2/227
|
0.43%
1/231
|
|
Skin and subcutaneous tissue disorders
Edema - Lower Extremities
|
0.44%
1/227
|
1.7%
4/231
|
|
Skin and subcutaneous tissue disorders
Burning Sensation
|
1.8%
4/227
|
1.3%
3/231
|
|
Skin and subcutaneous tissue disorders
Rash - NOS
|
0.88%
2/227
|
3.0%
7/231
|
|
Skin and subcutaneous tissue disorders
Rash - Lower Extremities
|
2.2%
5/227
|
0.43%
1/231
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
1.8%
4/227
|
0.43%
1/231
|
|
Skin and subcutaneous tissue disorders
Skin Ulcerations
|
0.44%
1/227
|
0.43%
1/231
|
|
Skin and subcutaneous tissue disorders
Rosacea
|
0.88%
2/227
|
0.43%
1/231
|
|
Skin and subcutaneous tissue disorders
Feeling of Tightness / Flusing in Feet
|
0.88%
2/227
|
0.00%
0/231
|
|
Immune system disorders
Allergic Rhinitis
|
2.2%
5/227
|
0.87%
2/231
|
|
Immune system disorders
Red and Crusty Eye
|
0.44%
1/227
|
0.00%
0/231
|
|
Immune system disorders
Nasal Congestion
|
0.44%
1/227
|
1.3%
3/231
|
|
Cardiac disorders
Hypertension
|
2.2%
5/227
|
2.2%
5/231
|
|
Cardiac disorders
Cardiac Arrythmia
|
0.44%
1/227
|
0.43%
1/231
|
|
Cardiac disorders
Increased Heart Rate
|
0.88%
2/227
|
0.43%
1/231
|
|
Cardiac disorders
Congestive Heart Failure
|
0.44%
1/227
|
0.00%
0/231
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.44%
1/227
|
0.43%
1/231
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.44%
1/227
|
0.43%
1/231
|
|
Metabolism and nutrition disorders
Hypoalbumin
|
0.44%
1/227
|
0.43%
1/231
|
|
Metabolism and nutrition disorders
Hypotension
|
0.44%
1/227
|
0.00%
0/231
|
|
Metabolism and nutrition disorders
Hypomagnesium
|
0.00%
0/227
|
0.43%
1/231
|
|
Endocrine disorders
Diabetes
|
0.00%
0/227
|
0.87%
2/231
|
|
Endocrine disorders
Hypothyroidism
|
0.88%
2/227
|
0.43%
1/231
|
|
Endocrine disorders
Hyperglycemia
|
2.6%
6/227
|
0.87%
2/231
|
|
Endocrine disorders
Hypercholestremia
|
0.00%
0/227
|
0.43%
1/231
|
|
Endocrine disorders
Hyperlipidemia
|
0.44%
1/227
|
0.00%
0/231
|
|
Reproductive system and breast disorders
Urinary Tract Infection
|
0.88%
2/227
|
1.3%
3/231
|
|
Reproductive system and breast disorders
Benign Prostate Hyperplasia
|
0.00%
0/227
|
0.43%
1/231
|
|
Reproductive system and breast disorders
Bladder Spasms, Occasional
|
0.44%
1/227
|
0.00%
0/231
|
|
Blood and lymphatic system disorders
Anemia
|
1.3%
3/227
|
0.43%
1/231
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.44%
1/227
|
0.00%
0/231
|
|
Infections and infestations
Head Cold
|
0.44%
1/227
|
0.87%
2/231
|
|
Infections and infestations
Otitis Media
|
0.44%
1/227
|
0.00%
0/231
|
|
General disorders
Headache
|
1.8%
4/227
|
1.3%
3/231
|
|
Psychiatric disorders
Anxiety
|
0.44%
1/227
|
2.6%
6/231
|
|
Psychiatric disorders
Depression
|
0.44%
1/227
|
0.87%
2/231
|
|
Gastrointestinal disorders
Nausea
|
0.88%
2/227
|
3.0%
7/231
|
|
Gastrointestinal disorders
Vomiting
|
0.88%
2/227
|
1.7%
4/231
|
|
Gastrointestinal disorders
Abdominal Pain
|
1.3%
3/227
|
0.00%
0/231
|
|
Gastrointestinal disorders
Diarrhea
|
0.88%
2/227
|
2.6%
6/231
|
|
Gastrointestinal disorders
Dysphagia
|
0.44%
1/227
|
0.43%
1/231
|
|
Gastrointestinal disorders
Dyspepsia
|
1.3%
3/227
|
1.7%
4/231
|
|
Gastrointestinal disorders
Constipation
|
0.44%
1/227
|
1.7%
4/231
|
|
Gastrointestinal disorders
GI Fistula
|
0.44%
1/227
|
0.00%
0/231
|
|
Gastrointestinal disorders
GERD
|
0.88%
2/227
|
0.00%
0/231
|
|
Gastrointestinal disorders
Mucositis
|
0.44%
1/227
|
0.43%
1/231
|
|
Gastrointestinal disorders
Black Tarry Stool
|
0.00%
0/227
|
0.43%
1/231
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.8%
4/227
|
3.0%
7/231
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
1.3%
3/227
|
1.7%
4/231
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.88%
2/227
|
2.2%
5/231
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.44%
1/227
|
1.3%
3/231
|
|
Nervous system disorders
Migraine
|
1.3%
3/227
|
0.43%
1/231
|
|
Nervous system disorders
Neuropathy
|
2.6%
6/227
|
3.5%
8/231
|
|
Nervous system disorders
Ataxia
|
0.44%
1/227
|
0.00%
0/231
|
|
Nervous system disorders
Cramps
|
0.88%
2/227
|
0.87%
2/231
|
|
Nervous system disorders
Restless Leg Syndrome
|
1.8%
4/227
|
0.00%
0/231
|
|
Musculoskeletal and connective tissue disorders
Pain Lower Extremities
|
2.2%
5/227
|
6.1%
14/231
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.6%
6/227
|
4.8%
11/231
|
|
Musculoskeletal and connective tissue disorders
Pain in Joint
|
2.2%
5/227
|
1.7%
4/231
|
|
Musculoskeletal and connective tissue disorders
Pain Upper Extremities
|
0.88%
2/227
|
1.7%
4/231
|
|
Musculoskeletal and connective tissue disorders
Pain in Bone
|
1.3%
3/227
|
0.00%
0/231
|
|
Musculoskeletal and connective tissue disorders
Pain in Knee
|
1.8%
4/227
|
0.87%
2/231
|
|
Musculoskeletal and connective tissue disorders
Pain in Head / Neck
|
1.8%
4/227
|
1.3%
3/231
|
|
Musculoskeletal and connective tissue disorders
Pain in Back
|
0.88%
2/227
|
0.00%
0/231
|
Additional Information
Charles E. Heckler, PhD, MS. Research Assistant Professor
University of Rochester Medical Center
Phone: 585-273-1141
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place