A study to test pregabalin in the treatment of patients with painful diabetic peripheral neuropathy and pain on walking

• Register: EUCTR
• Last refreshed on: 17 March 2014
• Main ID: EUCTR2011-003266-32-SE
• Date of registration: 17/10/2011
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, NY 10017
• Public title: A study to test pregabalin in the treatment of patients with painful diabetic peripheral neuropathy and pain on walking
• Scientific title: A PHASE 3B MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED CROSS-OVER EFFICACY AND SAFETY STUDY OF PREGABALIN IN THE TREATMENT OF PATIENTS WITH PAINFUL DIABETIC PERIPHERAL NEUROPATHY AND PAIN ON WALKING (PROTOCOL A0081269)
• Date of first enrolment: 21/12/2011
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-003266-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Czech Republic, South Africa, Sweden, United States

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study;
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including the training and completion of the daily pain and sleep diaries using the IVRS system;
3. Men or women who are at least 18 years of age;
4. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
5. Diagnosis of type 1 or 2 diabetes mellitus with current hemoglobin A1C levels of =11%. If the subject is on an antidiabetic medication regimen, it must be stable for the 30 days prior to Visit 2/Randomization;
6. Diagnosis of painful, diabetic distal symmetrical sensorimotor, polyneuropathy for at least 3 months; (refer to Appendix 1 of the protocol for Diagnostic Worksheet for DPN);
7. Ability to walk 50 feet (15.2 m) on a flat surface unassisted.
8. Meet the following 2 criteria demonstrating inadequate pain control:
• At Visit 1, Screening, a score of =4 on the one-week recall, 0-10-point numerical rating scale (Weekly-Pain NRS)
• At Visit 2/Randomization, subjects must have completed at least 4 daily pain diaries over the past 7 days (baseline) and have an average daily DPN pain score of =4 on the 0-10 point numeric rating scale (daily pain diary).
9. Meet all of the following criteria demonstrating pain on walking after the walk test. The walk test will consist of walking 50 feet (15.2 meters) on a flat surface with one turn allowed, ie, 25 feet in one direction and then return), and then immediate completion of the DPN pain on walking NRS:
• A post-walk pain score of at least 4 or greater, at both V1/Screening and V2/Randomization.
• The post-walk pain score (DPN pain on walking NRS) must be greater than the pre-walk pain score at both V1/Screening and V2/Randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion criteria:
1. Have failed pregabalin treatment due to lack of efficacy at therapeutic doses, have intolerance to pregabalin or any pregabalin ingredient, or participated in a pregabalin clinical trial. If the subject has taken pregabalin and discontinued for reasons other than lack of efficacy or intolerance, then they will be eligible. Pregabalin use within the last 30 days (prior to V1) is not permitted;
2. A pain fluctuation of more than a 4 point difference from the highest to the lowest score during the baseline week as assessed by the daily pain diary;
3. Use of an aid while walking, difficulty with standing upright or inability to walk 50 feet;
4. Significant peripheral vascular disease (arterial or venous) causing pain on walking. History of intermittent claudication;
5. Neurological disorders unrelated to diabetic neuropathy that may confound the assessment of distal neuropathic pain (Refer to Appendix 1of the protocol);
6. Neurological or other disorders unrelated to diabetic neuropathy that might confound assessments of pain on walking (eg, spinal stenosis, active back pain or sciatica); vascular conditions or local foot conditions (eg, plantar fasciitis) or other conditions (eg, knee pain, arthritis) that could cause pain on walking;
7. Pain due to other conditions, that in the opinion of the investigator, may confound assessment or self-evaluation of the pain due to diabetic neuropathy;
8. Clinically significant unstable diabetes mellitus, or unstable hepatic, respiratory, or hematologic illnesses, unstable cardiovascular disease (including a myocardial infarction in the 3 months prior to Visit 1/Screening), or symptomatic peripheral vascular disease;
9. Any amputation of lower extremities, foot ulcers involving the great toes, or presence of significant pedal edema;
10. History or current evidence of any condition that could lead to impaired absorption of vitamin B12 (pernicious anemia, chronic gastritis of any cause, surgery such as gastrectomy or gastric bypass surgery, etc.).
11. A history of untreated hypothyroidism in the past 12 months, or HIV infection;
12. Have had a malignancy other than basal cell carcinoma or carcinoma in situ of the cervix within the past 5 years;
13. Have creatinine clearance (CLcr) =60 mL/min (estimated prior to Visit 2 from serum creatinine obtained at Visit 1, body weight, age, and gender using the Cockcroft and Gault equation; see Section 7.2.1.of the protocol. Subjects who have an estimated CLcr =60 mL/min by this screening method may have their CLcr measured, at the investigator’s discretion, with a 24 hour urine collection performed at the central laboratory. If this 24 hour urine CLcr is >60 mL/min, the subject will be considered eligible for this parameter;
14. Abnormal (clinically significant) electrocardiogram (ECG);
15. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study;
16. Currently receiving pregabalin or opioids for painful DPN. Subjects requiring opioid use are excluded. However, subjects may be eligible if opioids are washed out at least 4 weeks prior to V1 and following informed consent, if being discontinued as part of this study;
17. Use of prohibited conco

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Painful Diabetic Peripheral Neuropathy
MedDRA version: 14.1 Level: LLT Classification code 10012683 Term: Diabetic peripheral neuropathy System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Lyrica®
Product Name: Pregabalin
Product Code: N03AX16
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Other descriptive name: Pregabalin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Lyrica®
Product Name: Pregabalin
Product Code: N03AX16
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Other descriptive name: Pregabalin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Reduction in DPN pain, as from the daily pain diaries while receiving study medication in each treatment period
(V2-V6 & V7-V11)

Reduction in DPN on walking, completed before and immediately after walking 50ft (15.2m) on a flat surface
(V1, V2, V5, V6/ET, V10 & V11/ET)

Main Objective: There are two co-primary objectives for this study. In patients with painful DPN, to evaluate the efficacy of pregabalin compared to placebo in:
1. The reduction in DPN pain; and
2. The reduction in DPN pain on walking.

Secondary Objective: In addition, the study will assess if pregabalin provides other benefits associated with improved functional outcomes (secondary objectives). The safety and tolerability of pregabalin will also be evaluated.

Primary end point(s): Primary Efficacy Endpoints:
• Reduction in DPN pain, as assessed by the endpoint mean pain score based on the mean of the last 7 daily pain numeric rating scale (NRS) scores from the daily pain diaries while receiving study medication in each treatment period (daily pain diary, 0-10 point NRS).
• Reduction in DPN pain on walking as assessed by the subject’s report of DPN pain on walking, using a 0-10 point NRS, that is completed immediately after walking 50 ft (15.2 m) on a flat surface (DPN pain on walking NRS).

Secondary Outcome(s)

Secondary end point(s): Secondary Efficacy Endpoints:
• Responder rate based on a 30% and 50% improvement in mean pain response (from daily pain diary);
• Brief Pain Inventory-short form (BPI-sf);
• Actigraph device worn on hip during waking hours (to measure steps and daytime activity);
• Walk-12;
• Norfolk Quality of Life Questionnaire for Diabetic Neuropathy (QOL-DN) modified with 2 week recall;
• Patient Global Impression of Change (PGIC), assessed at the end of period 1 compared to the start of treatment;
• Sleep Interference Rating Scale (daily sleep diary);
• Hospital Anxiety and Depression Scale (HADS);
• Euro QoL-5 Dimensions (EQ-5D).

Timepoint(s) of evaluation of this end point: • Responder rate based on a 30% and 50% improvement in mean pain response (from daily pain diary) (V2-V6 & V7-V11);
• Brief Pain Inventory-short form (BPI-sf) - V2, V6/ET & V11/ET;
• Actigraph device worn on hip during waking hours (to measure steps and daytime activity) - V2, V6/ET & V11/ET
• Walk-12 (V2, V6/ET & V11/ET);
• Norfolk Quality of Life Questionnaire for Diabetic Neuropathy (QOL-DN) modified with 2 week recall (V2, V6/ET & V11/ET);
• Patient Global Impression of Change (PGIC), assessed at the end of period 1 compared to the start of treatment (V6/ET & V11/ET);
• Sleep Interference Rating Scale (daily sleep diary) V1-V12:
• Hospital Anxiety and Depression Scale (HADS) V2, V6/ET & V11/ET
• Euro QoL-5 Dimensions (EQ-5D) V2, V6/ET & V11/ET .

Secondary ID(s)

A0081269

Source(s) of Monetary Support

Pfizer Inc