A Trial in Painful Diabetic Peripheral Neuropathy With GRT3983Y

• Sponsor: Grünenthal GmbH (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01056315
• Collaborator: (none)
• Enrollment: 553
• Locations: 61
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 9.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This trial is assessing the analgesic efficacy and safety of a new central analgesic in subjects with pain due to diabetic peripheral neuropathy (DPN).

Condition or Disease	Intervention/Treatment	Phase
Painful Diabetic Neuropathy	Drug: GRT3938Y; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 553 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Double-blind, Placebo-controlled, Parallel-group Trial to Assess the Analgesic Efficacy and Safety of a New Analgesic Compared to Placebo in Subjects With Painful Diabetic Peripheral Neuropathy
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A GRT3983Y Participants randomly assigned to receive GRT3983Y.	Drug: GRT3938Y; Overencapsulated tablets of GRT3983Y, 100 to 300mg daily dose, 16 weeks treatment.
Placebo Comparator: B Placebo Participants randomly assigned to placebo.	Drug: Placebo; Overencapsulated tablets of placebo, 16 weeks treatment.

Outcome Measures

Primary Outcome Measures

1. Average Pain Intensity [Baseline; last 7 days of 12-week maintenance]

   The primary efficacy endpoint is the change from baseline in the mean of the daily average pain intensity scores (on an 11-point NRS) over the last 7 days of the 12-week maintenance (Week 16).

Secondary Outcome Measures

1. Change From Baseline in the Mean of the Daily Average Pain Intensity Scores (on an 11-point NRS) Over the Entire 12-week Maintenance [Baseline, Daily scores over entire 12 week maintenance]

2. Proportion of Subjects Achieving Various Levels of Pain Improvement (Including 30% and 50%) Based on the Percent Change From Baseline to the Last 7 Days of the 12-week Maintenance on an 11-point NRS (Responder Analysis). [Baseline, Last 7 days of 12-week maintenance]

3. Change From Baseline in the Mean of the Daily Average Pain Intensity Scores (on an 11-point NRS) Over Each Week of Maintenance. [Baseline; daily scores over each week of maintenance]

4. Change From Baseline of the Weekly Mean of Night Pain Intensity (on an 11-point NRS). [Baseline; weekly mean]

5. Change From Baseline of the Weekly Mean of Current Pain Intensity (on an 11-point NRS) in the Evening and in the Morning, Respectively. [Baseline, weekly mean]

6. Brief Pain Inventory Scores: Changes From Baseline to Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, and Day 113 (Final Visit). [Baseline, weekly mean]

7. Neuropathic Pain Symptoms Inventory: Changes From Baseline to Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99 and Day 113 (Final Visit) [Baseline, weekly mean]

8. Patient Global Impression of Change Using a 7-point Verbal Rating Scale, on Day 29, Day 71 and Day 113 (Final Visit). [Day 29, Day 71 and Day 113.]

9. Short Form 36 Health Survey (SF-36®): Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit). [Baseline, Day 29, Day 71 and Day 113.]

10. EuroQol-5 Dimension Health Questionnaire: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit). [Baseline, Day 29, Day 71 and Day 113.]

11. Assessment of Each Item of the Leeds Sleep Evaluation Questionnaire: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit). [Baseline, Day 29, Day 71 and Day 113.]

12. Hospital Anxiety and Depression Scale: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit). [Baseline, Day 29, Day 71 and Day 113.]

13. Time to Treatment Discontinuation Due to Lack of Efficacy. [Baseline to time to treatment discontinuation]

14. Assessment of Rescue Medication Usage During the 4-week Titration. [4-week titration phase]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Symmetrical painful diabetic peripheral neuropathy

Exclusion Criteria:

• History of hypersensitivity, allergy or contraindication to opioids and acetaminophen

• Confounding painful conditions

• Significant vascular disease

• History or risk of seizure

• Chronic disease that might effect drug absorption, distribution, metabolism, or excretion

• Female subjects who are being pregnant or breastfeeding

• Evidence or history of alcohol, medication, or drug abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 127	Fairhope	Alabama	United States
2	Site 130	Homewood	Alabama	United States
3	Site 112	Tucson	Arizona	United States
4	Site 129	Escondido	California	United States
5	Site 209	Fullerton	California	United States
6	Site 135	Long Beach	California	United States
7	Site 202	Northridge	California	United States
8	Site 208	Northridge	California	United States
9	Site 219	Northridge	California	United States
10	Site 203	San Francisco	California	United States
11	Site 116	Santa Ana	California	United States
12	Site 118	Santa Ana	California	United States
13	Site 121	Santa Ana	California	United States
14	Site 133	Santa Ana	California	United States
15	Site 126	Vista	California	United States
16	Site 214	Vista	California	United States
17	Site 201	Waterbury	Connecticut	United States
18	Site 136	Deerfield Beach	Florida	United States
19	Site 137	Deerfield Beach	Florida	United States
20	Site 140	Deerfield Beach	Florida	United States
21	Site 216	Deerfield Beach	Florida	United States
22	Site 217	Deerfield Beach	Florida	United States
23	Site 218	Deerfield Beach	Florida	United States
24	Site 117	Fort Myers	Florida	United States
25	Site 124	Jacksonville	Florida	United States
26	Site 228	Jupiter	Florida	United States
27	Site 101	Orlando	Florida	United States
28	Site 226	Orlando	Florida	United States
29	Site 206	Sarasota	Florida	United States
30	Site 212	West Palm Beach	Florida	United States
31	Site 142	Atlanta	Georgia	United States
32	Site 128	Chicago	Illinois	United States
33	Site 223	Chicago	Illinois	United States
34	Site 114	Leawood	Kansas	United States
35	Site 102	Paducah	Kentucky	United States
36	Site 211	Baltimore	Maryland	United States
37	Site 108	East Bridgewater	Massachusetts	United States
38	Site 113	Las Vegas	Nevada	United States
39	Site 122	Princeton	New Jersey	United States
40	Site 230	New York	New York	United States
41	Site 109	Rochester	New York	United States
42	Site 225	Asheville	North Carolina	United States
43	Site 115	High Point	North Carolina	United States
44	Site 227	Canton	Ohio	United States
45	Site 233	Cincinnati	Ohio	United States
46	Site 111	Toledo	Ohio	United States
47	Site 125	Toledo	Ohio	United States
48	Site 104	Philadelphia	Pennsylvania	United States
49	Site 106	Philadelphia	Pennsylvania	United States
50	Site 205	Philadelphia	Pennsylvania	United States
51	Site 105	Austin	Texas	United States
52	Site 213	Corpus Christi	Texas	United States
53	Site 110	Houston	Texas	United States
54	Site 123	Houston	Texas	United States
55	Site 204	Houston	Texas	United States
56	Site 210	Houston	Texas	United States
57	Site 231	Houston	Texas	United States
58	Site 131	San Antonio	Texas	United States
59	Site 215	San Antonio	Texas	United States
60	Site 221	San Antonio	Texas	United States
61	Site 139	Provo	Utah	United States

Sponsors and Collaborators

• Grünenthal GmbH

Investigators

• Study Director: Study Director, Grünenthal GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Grünenthal GmbH
• ClinicalTrials.gov Identifier: NCT01056315
• Other Study ID Numbers: 131885
• First Posted: Jan 26, 2010
• Last Update Posted: Oct 28, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by Grünenthal GmbH: Analgesia; Diabetic Neuropathy; Neuropathic pain; Painful; Chronic pain
• Additional relevant MeSH terms: Peripheral Nervous System Diseases; Diabetic Neuropathies; Pain

Study Results

Participant Flow

Pre-assignment Detail	503 participants were excluded from the trial before assignment to a treatment group because they did not meet the inclusion and or exclusion criteria.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description
Period Title: Overall Study
STARTED	27	23
COMPLETED	13	12
NOT COMPLETED	14	11

Baseline Characteristics

Arm/Group Title	GRT3983Y	Placebo	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	27	23	50
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	20 74.1%	14 60.9%	34 68%
>=65 years	7 25.9%	9 39.1%	16 32%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.38 (8.942)	60.27 (10.438)	59.79 (9.568)
Sex: Female, Male (Count of Participants)
Female	12 44.4%	8 34.8%	20 40%
Male	15 55.6%	15 65.2%	30 60%
Region of Enrollment (participants) [Number]
United States	27 100%	23 100%	50 100%

Outcome Measures

1. Primary Outcome

Title	Average Pain Intensity
Description	The primary efficacy endpoint is the change from baseline in the mean of the daily average pain intensity scores (on an 11-point NRS) over the last 7 days of the 12-week maintenance (Week 16).
Time Frame	Baseline; last 7 days of 12-week maintenance

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

2. Secondary Outcome

Title	Change From Baseline in the Mean of the Daily Average Pain Intensity Scores (on an 11-point NRS) Over the Entire 12-week Maintenance
Time Frame	Baseline, Daily scores over entire 12 week maintenance

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

3. Secondary Outcome

Title	Proportion of Subjects Achieving Various Levels of Pain Improvement (Including 30% and 50%) Based on the Percent Change From Baseline to the Last 7 Days of the 12-week Maintenance on an 11-point NRS (Responder Analysis).
Time Frame	Baseline, Last 7 days of 12-week maintenance

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

4. Secondary Outcome

Title	Change From Baseline in the Mean of the Daily Average Pain Intensity Scores (on an 11-point NRS) Over Each Week of Maintenance.
Time Frame	Baseline; daily scores over each week of maintenance

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

5. Secondary Outcome

Title	Change From Baseline of the Weekly Mean of Night Pain Intensity (on an 11-point NRS).
Time Frame	Baseline; weekly mean

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

6. Secondary Outcome

Title	Change From Baseline of the Weekly Mean of Current Pain Intensity (on an 11-point NRS) in the Evening and in the Morning, Respectively.
Time Frame	Baseline, weekly mean

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

7. Secondary Outcome

Title	Brief Pain Inventory Scores: Changes From Baseline to Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, and Day 113 (Final Visit).
Time Frame	Baseline, weekly mean

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

8. Secondary Outcome

Title	Neuropathic Pain Symptoms Inventory: Changes From Baseline to Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99 and Day 113 (Final Visit)
Time Frame	Baseline, weekly mean

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

9. Secondary Outcome

Title	Patient Global Impression of Change Using a 7-point Verbal Rating Scale, on Day 29, Day 71 and Day 113 (Final Visit).
Time Frame	Day 29, Day 71 and Day 113.

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

10. Secondary Outcome

Title	Short Form 36 Health Survey (SF-36®): Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit).
Time Frame	Baseline, Day 29, Day 71 and Day 113.

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

11. Secondary Outcome

Title	EuroQol-5 Dimension Health Questionnaire: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit).
Time Frame	Baseline, Day 29, Day 71 and Day 113.

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

12. Secondary Outcome

Title	Assessment of Each Item of the Leeds Sleep Evaluation Questionnaire: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit).
Time Frame	Baseline, Day 29, Day 71 and Day 113.

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

13. Secondary Outcome

Title	Hospital Anxiety and Depression Scale: Changes From Baseline to Day 29, Day 71 and Day 113 (Final Visit).
Time Frame	Baseline, Day 29, Day 71 and Day 113.

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

14. Secondary Outcome

Title	Time to Treatment Discontinuation Due to Lack of Efficacy.
Time Frame	Baseline to time to treatment discontinuation

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

15. Secondary Outcome

Title	Assessment of Rescue Medication Usage During the 4-week Titration.
Time Frame	4-week titration phase

Outcome Measure Data

Analysis Population Description

Efficacy data were not analyzed because of the limited number of subjects with efficacy data at the time of the early termination of the trial.

Arm/Group Title	GRT3983Y	Placebo
Arm/Group Description	Participants randomly assigned to receive GRT3983Y.	Participants randomly assigned to receive placebo.
Measure Participants	0	0

Adverse Events

Arm/Group Title	GRT3983Y		Placebo
Arm/Group Description
All Cause Mortality
	GRT3983Y		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	GRT3983Y		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/27 (7.4%)		1/23 (4.3%)
Cardiac disorders
Coronary artery disease	1/27 (3.7%)	1	0/23 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	0/27 (0%)	0	1/23 (4.3%)	1
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/27 (3.7%)	1	0/23 (0%)	0
Other (Not Including Serious) Adverse Events
	GRT3983Y		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/27 (55.6%)		14/23 (60.9%)
Gastrointestinal disorders
Nausea	10/27 (37%)	13	3/23 (13%)	3
Constipation	4/27 (14.8%)	5	2/23 (8.7%)	2
Vomiting	2/27 (7.4%)	2	0/23 (0%)	0
Abdominal pain	1/27 (3.7%)	1	3/23 (13%)	3
Diarrhoea	0/27 (0%)	0	3/23 (13%)	3
Infections and infestations
Upper respiratory tract infection	1/27 (3.7%)	1	3/23 (13%)	3
Musculoskeletal and connective tissue disorders
Back pain	0/27 (0%)	0	2/23 (8.7%)	2
Nervous system disorders
Dizziness	4/27 (14.8%)	4	1/23 (4.3%)	1
Somnolence	4/27 (14.8%)	5	1/23 (4.3%)	2
Headache	3/27 (11.1%)	4	2/23 (8.7%)	2
Hypoaesthesia	0/27 (0%)	0	2/23 (8.7%)	2
Psychiatric disorders
Insomnia	2/27 (7.4%)	2	0/23 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/27 (0%)	0	3/23 (13%)	3
Skin and subcutaneous tissue disorders
Pruritus	2/27 (7.4%)	2	1/23 (4.3%)	1
Rash	2/27 (7.4%)	2	0/23 (0%)	0

Limitations/Caveats

No participants were analyzed as the study was terminated

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

It is the Institution and Principal Investigator's obligation not to publish any information declaration, invention or whatsoever which is in connection with this Agreement without the prior written consent of the Sponsor.