A Long-Term Study To Evaluate Safety And Efficacy Of Pregabalin For Pain Associated With Diabetic Peripheral Neuropathy

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00553280
• Collaborator: (none)
• Enrollment: 123
• Locations: 27
• Arm: 1
• Duration (Months): 23
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and efficacy of the long-term use of pregabalin at doses up to 600 mg/day in patients with painful diabetic peripheral neuropathy who have completed 13 weeks of dosing in Study A0081163

Condition or Disease	Intervention/Treatment	Phase
Diabetic Neuropathy, Painful	Drug: pregabalin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 123 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Extension Safety And Efficacy Study Of Pregabalin (CI-1008) For Pain Associated With Diabetic Peripheral Neuropathy
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: pregabalin	Drug: pregabalin; Dosage: 150-600 mg/day (75-300 mg bid), oral administration, Treatment duration: 52 weeks

Outcome Measures

Primary Outcome Measures

1. Summary of Adverse Events [53 weeks]

   Number of participants with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Participants are counted only once per treatment in each row.

Secondary Outcome Measures

1. Change From Baseline in Short-Form McGill Pain Questionnaire: Sensory Scores [From baseline to 52 weeks or study discontinuation (Study Endpoint)]

   The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Sensory score ranges from 0-33. Higher scores indicate more severe pain.

2. Change From Baseline in Short-Form McGill Pain Questionnaire: Affective Scores [From baseline to 52 weeks or study discontinuation (Study Endpoint)]

   The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Affective score ranges from 0-12. Higher scores indicate more severe pain.

3. Change From Baseline in Short-Form McGill Pain Questionnaire: Total Scores [From baseline to 52 weeks or study discontinuation (Study Endpoint)]

   The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Total score ranges from 0-45. Higher scores indicate more severe pain.

4. Change From Baseline in Short-Form McGill Pain Questionnaire: Visual Analogue Scale Scores [From baseline to 52 weeks or study discontinuation (Study Endpoint)]

   The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Visual Analogue Scale Score ranges from 0-100 mm. Higher scores indicate more severe pain.

5. Change From Baseline in Short-Form McGill Pain Questionnaire: Present Pain Intensity Scores [From baseline to 52 weeks or study discontinuation (Study Endpoint)]

   The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Present pain intensity score ranges from 0-5. Higher scores indicate more severe pain.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients who completed the 13-week treatment of painful diabetic peripheral neuropathy in Study A0081163.

• Patients must be able to understand and cooperate with study procedures and have signed a written informed consent prior to entering the study

Exclusion Criteria:

• Patients who experienced serious adverse events in the preceding study (A0081163) that were determined by the investigator or the study sponsor to be causally related to the study medication.

• Patients exhibiting treatment non-compliance in the preceding study (A0081163)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Nagoya	Aichi	Japan
2	Pfizer Investigational Site	Date-shi	Fukushima	Japan
3	Pfizer Investigational Site	Nihonmatsu	Fukushima	Japan
4	Pfizer Investigational Site	Shirakawa-shi	Fukushima	Japan
5	Pfizer Investigational Site	Sukagawa	Fukushima	Japan
6	Pfizer Investigational Site	Kamakura	Kanagawa	Japan
7	Pfizer Investigational Site	Yokohama	Kanagawa	Japan
8	Pfizer Investigational Site	Sendai	Miyagi	Japan
9	Pfizer Investigational Site	Matsumoto	Nagano	Japan
10	Pfizer Investigational Site	Ueda	Nagano	Japan
11	Pfizer Investigational Site	Beppu	Oita	Japan
12	Pfizer Investigational Site	Yamada	Okayama	Japan
13	Pfizer Investigational Site	Naha	Okinawa	Japan
14	Pfizer Investigational Site	Tomishiro	Okinawa	Japan
15	Pfizer Investigational Site	Urazoe	Okinawa	Japan
16	Pfizer Investigational Site	Hirano-ku	Osaka	Japan
17	Pfizer Investigational Site	Suminoe-ku	Osaka	Japan
18	Pfizer Investigational Site	Sunto-gun	Shizuoka	Japan
19	Pfizer Investigational Site	Oyama-shi	Tochigi	Japan
20	Pfizer Investigational Site	Arakawa	Tokyo	Japan
21	Pfizer Investigational Site	Bunkyo-ku	Tokyo	Japan
22	Pfizer Investigational Site	Chiyoda-ku	Tokyo	Japan
23	Pfizer Investigational Site	Ohta-ku	Tokyo	Japan
24	Pfizer Investigational Site	Shibuya-ku	Tokyo	Japan
25	Pfizer Investigational Site	Fukuoka		Japan
26	Pfizer Investigational Site	Oita		Japan
27	Pfizer Investigational Site	Tokushima		Japan

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT00553280
• Other Study ID Numbers: A0081164
• First Posted: Nov 4, 2007
• Last Update Posted: Jan 25, 2021
• Last Verified: Apr 1, 2011

• Additional relevant MeSH terms: Peripheral Nervous System Diseases; Diabetic Neuropathies; Pregabalin

Study Results

Participant Flow

Recruitment Details	Thirty-six (36) centers in Japan
Pre-assignment Detail	Patients with pain associated with diabetic peripheral neuropathy who had completed the 13-week treatment phase in the preceding study (Study A0081163: NCT00553475), without any treatment-related serious adverse events or any compliance problems were eligible for the study.

Arm/Group Title	Pregabalin
Arm/Group Description	Participants initiated to take the study drug at a dose of 75 mg in the evening of Day 1, and then 150 mg/day (75 mg BID) for 1 week from Day 2. Thereafter, participants continued the treatment with pregabalin for 52 weeks, with the maximum doses of 300 mg/day (150 mg BID) for participants with low CLcr (30 < CLcr ≤ 60 mL/min) and 600 mg/day (300 mg BID) for participants with normal CLcr (CLcr > 60 mL/min). In consideration of safety and the effect on pain, the doses were adjusted by one step (150 mg/day) at each visit. Participants treated with pregabalin at the doses of 300 mg/day or higher ended the treatment after a 1-week dose reduction period.
Period Title: Overall Study
STARTED	123
COMPLETED	97
NOT COMPLETED	26

Baseline Characteristics

Arm/Group Title	Pregabalin
Arm/Group Description	Participants initiated to take the study drug at a dose of 75 mg in the evening of Day 1, and then 150 mg/day (75 mg BID) for 1 week from Day 2. Thereafter, participants continued the treatment with pregabalin for 52 weeks, with the maximum doses of 300 mg/day (150 mg BID) for participants with low CLcr (30 < CLcr ≤ 60 mL/min) and 600 mg/day (300 mg BID) for participants with normal CLcr (CLcr > 60 mL/min). In consideration of safety and the effect on pain, the doses were adjusted by one step (150 mg/day) at each visit. Participants treated with pregabalin at the doses of 300 mg/day or higher ended the treatment after a 1-week dose reduction period.
Overall Participants	123
Age, Customized (participants) [Number]
< 18 years	0 0%
18 - 44 years	6 4.9%
45 - 64 years	71 57.7%
>= 65 years	46 37.4%
Age, Customized (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.7 (10.0)
Sex: Female, Male (Count of Participants)
Female	23 18.7%
Male	100 81.3%

Outcome Measures

1. Primary Outcome

Title	Summary of Adverse Events
Description	Number of participants with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Participants are counted only once per treatment in each row.
Time Frame	53 weeks

Outcome Measure Data

Analysis Population Description

Safety analysis set: all participants who had received at least one dose of the study drug.

Arm/Group Title	Pregabalin
Arm/Group Description	Participants initiated to take the study drug at a dose of 75 mg in the evening of Day 1, and then 150 mg/day (75 mg BID) for 1 week from Day 2. Thereafter, participants continued the treatment with pregabalin for 52 weeks, with the maximum doses of 300 mg/day (150 mg BID) for participants with low CLcr (30 < CLcr ≤ 60 mL/min) and 600 mg/day (300 mg BID) for participants with normal CLcr (CLcr > 60 mL/min). In consideration of safety and the effect on pain, the doses were adjusted by one step (150 mg/day) at each visit. Participants treated with pregabalin at the doses of 300 mg/day or higher ended the treatment after a 1-week dose reduction period.
Measure Participants	123
Participants with adverse events	114 92.7%
Participants with serious adverse events	21 17.1%
Participants with severe adverse events	7 5.7%
Participants discontinued due to adverse events	17 13.8%
Dose reduced or temporary discontinuation	43 35%

2. Secondary Outcome

Title	Change From Baseline in Short-Form McGill Pain Questionnaire: Sensory Scores
Description	The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Sensory score ranges from 0-33. Higher scores indicate more severe pain.
Time Frame	From baseline to 52 weeks or study discontinuation (Study Endpoint)

Outcome Measure Data

Analysis Population Description

Full analysis set. No imputations for missing data.

Arm/Group Title	Pregabalin
Arm/Group Description	Participants initiated to take the study drug at a dose of 75 mg in the evening of Day 1, and then 150 mg/day (75 mg BID) for 1 week from Day 2. Thereafter, participants continued the treatment with pregabalin for 52 weeks, with the maximum doses of 300 mg/day (150 mg BID) for participants with low CLcr (30 < CLcr ≤ 60 mL/min) and 600 mg/day (300 mg BID) for participants with normal CLcr (CLcr > 60 mL/min). In consideration of safety and the effect on pain, the doses were adjusted by one step (150 mg/day) at each visit. Participants treated with pregabalin at the doses of 300 mg/day or higher ended the treatment after a 1-week dose reduction period.
Measure Participants	123
Mean (Standard Deviation) [score on scale]	-3.5 (5.1)

3. Secondary Outcome

Title	Change From Baseline in Short-Form McGill Pain Questionnaire: Affective Scores
Description	The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Affective score ranges from 0-12. Higher scores indicate more severe pain.
Time Frame	From baseline to 52 weeks or study discontinuation (Study Endpoint)

Outcome Measure Data

Analysis Population Description

Full analysis set. No imputations for missing data.

Arm/Group Title	Pregabalin
Arm/Group Description	Participants initiated to take the study drug at a dose of 75 mg in the evening of Day 1, and then 150 mg/day (75 mg BID) for 1 week from Day 2. Thereafter, participants continued the treatment with pregabalin for 52 weeks, with the maximum doses of 300 mg/day (150 mg BID) for participants with low CLcr (30 < CLcr ≤ 60 mL/min) and 600 mg/day (300 mg BID) for participants with normal CLcr (CLcr > 60 mL/min). In consideration of safety and the effect on pain, the doses were adjusted by one step (150 mg/day) at each visit. Participants treated with pregabalin at the doses of 300 mg/day or higher ended the treatment after a 1-week dose reduction period.
Measure Participants	123
Mean (Standard Deviation) [score on scale]	-1.2 (2.4)

4. Secondary Outcome

Title	Change From Baseline in Short-Form McGill Pain Questionnaire: Total Scores
Description	The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Total score ranges from 0-45. Higher scores indicate more severe pain.
Time Frame	From baseline to 52 weeks or study discontinuation (Study Endpoint)

Outcome Measure Data

Analysis Population Description

Full analysis set. No imputations for missing data.

Arm/Group Title	Pregabalin
Arm/Group Description	Participants initiated to take the study drug at a dose of 75 mg in the evening of Day 1, and then 150 mg/day (75 mg BID) for 1 week from Day 2. Thereafter, participants continued the treatment with pregabalin for 52 weeks, with the maximum doses of 300 mg/day (150 mg BID) for participants with low CLcr (30 < CLcr ≤ 60 mL/min) and 600 mg/day (300 mg BID) for participants with normal CLcr (CLcr > 60 mL/min). In consideration of safety and the effect on pain, the doses were adjusted by one step (150 mg/day) at each visit. Participants treated with pregabalin at the doses of 300 mg/day or higher ended the treatment after a 1-week dose reduction period.
Measure Participants	123
Mean (Standard Deviation) [score on scale]	-4.7 (6.8)

5. Secondary Outcome

Title	Change From Baseline in Short-Form McGill Pain Questionnaire: Visual Analogue Scale Scores
Description	The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Visual Analogue Scale Score ranges from 0-100 mm. Higher scores indicate more severe pain.
Time Frame	From baseline to 52 weeks or study discontinuation (Study Endpoint)

Outcome Measure Data

Analysis Population Description

Full analysis set. No imputations for missing data.

Arm/Group Title	Pregabalin
Arm/Group Description	Participants initiated to take the study drug at a dose of 75 mg in the evening of Day 1, and then 150 mg/day (75 mg BID) for 1 week from Day 2. Thereafter, participants continued the treatment with pregabalin for 52 weeks, with the maximum doses of 300 mg/day (150 mg BID) for participants with low CLcr (30 < CLcr ≤ 60 mL/min) and 600 mg/day (300 mg BID) for participants with normal CLcr (CLcr > 60 mL/min). In consideration of safety and the effect on pain, the doses were adjusted by one step (150 mg/day) at each visit. Participants treated with pregabalin at the doses of 300 mg/day or higher ended the treatment after a 1-week dose reduction period.
Measure Participants	123
Mean (Standard Deviation) [mm]	-25.4 (26.4)

6. Secondary Outcome

Title	Change From Baseline in Short-Form McGill Pain Questionnaire: Present Pain Intensity Scores
Description	The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Present pain intensity score ranges from 0-5. Higher scores indicate more severe pain.
Time Frame	From baseline to 52 weeks or study discontinuation (Study Endpoint)

Outcome Measure Data

Analysis Population Description

Full analysis set. No imputations for missing data.

Arm/Group Title	Pregabalin
Arm/Group Description	Participants initiated to take the study drug at a dose of 75 mg in the evening of Day 1, and then 150 mg/day (75 mg BID) for 1 week from Day 2. Thereafter, participants continued the treatment with pregabalin for 52 weeks, with the maximum doses of 300 mg/day (150 mg BID) for participants with low CLcr (30 < CLcr ≤ 60 mL/min) and 600 mg/day (300 mg BID) for participants with normal CLcr (CLcr > 60 mL/min). In consideration of safety and the effect on pain, the doses were adjusted by one step (150 mg/day) at each visit. Participants treated with pregabalin at the doses of 300 mg/day or higher ended the treatment after a 1-week dose reduction period.
Measure Participants	123
Mean (Standard Deviation) [score on scale]	-0.7 (1.1)

Adverse Events

Time Frame	53 weeks
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Pregabalin
Arm/Group Description	Participants initiated to take the study drug at a dose of 75 mg in the evening of Day 1, and then 150 mg/day (75 mg BID) for 1 week from Day 2. Thereafter, participants continued the treatment with pregabalin for 52 weeks, with the maximum doses of 300 mg/day (150 mg BID) for participants with low CLcr (30 < CLcr ≤ 60 mL/min) and 600 mg/day (300 mg BID) for participants with normal CLcr (CLcr > 60 mL/min). In consideration of safety and the effect on pain, the doses were adjusted by one step (150 mg/day) at each visit. Participants treated with pregabalin at the doses of 300 mg/day or higher ended the treatment after a 1-week dose reduction period.
All Cause Mortality
	Pregabalin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pregabalin
	Affected / at Risk (%)	# Events
Total	21/123 (17.1%)
Cardiac disorders
Atrioventricular block complete	1/123 (0.8%)
Ear and labyrinth disorders
Meniere's disease	1/123 (0.8%)
Infections and infestations
Cellulitis	2/123 (1.6%)
Diabetic gangrene	1/123 (0.8%)
Pneumonia	3/123 (2.4%)
Injury, poisoning and procedural complications
Femoral neck fracture	1/123 (0.8%)
Femur fracture	1/123 (0.8%)
Hand fracture	1/123 (0.8%)
Thermal burn	1/123 (0.8%)
Investigations
Blood glucose abnormal	1/123 (0.8%)
Metabolism and nutrition disorders
Hyperglycaemia	1/123 (0.8%)
Hypoglycaemia	1/123 (0.8%)
Musculoskeletal and connective tissue disorders
Back pain	1/123 (0.8%)
Lumbar spinal stenosis	1/123 (0.8%)
Osteonecrosis	1/123 (0.8%)
Spinal osteoarthritis	1/123 (0.8%)
Spondylolisthesis	1/123 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma	1/123 (0.8%)
Nervous system disorders
Cerebral infarction	2/123 (1.6%)
Transient ischaemic attack	1/123 (0.8%)
Renal and urinary disorders
Renal impairment	1/123 (0.8%)
Other (Not Including Serious) Adverse Events
	Pregabalin
	Affected / at Risk (%)	# Events
Total	101/123 (82.1%)
Eye disorders
Diabetic retinopathy	9/123 (7.3%)
Visual acuity reduced	7/123 (5.7%)
Gastrointestinal disorders
Constipation	11/123 (8.9%)
Diarrhoea	8/123 (6.5%)
General disorders
Face oedema	10/123 (8.1%)
Oedema	9/123 (7.3%)
Oedema peripheral	21/123 (17.1%)
Infections and infestations
Nasopharyngitis	39/123 (31.7%)
Injury, poisoning and procedural complications
Contusion	8/123 (6.5%)
Fall	14/123 (11.4%)
Investigations
Weight increased	35/123 (28.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/123 (5.7%)
Pain in extremity	7/123 (5.7%)
Nervous system disorders
Dizziness	29/123 (23.6%)
Somnolence	30/123 (24.4%)
Skin and subcutaneous tissue disorders
Eczema	10/123 (8.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.