Safety and Efficacy of AEG33773 Versus Placebo in Patients With Painful Diabetic Peripheral Neuropathy

NCT00891683 | Completed Phase 2 DMC

• 1 other identifier: AEG33773-201
• Study Type: interventional
• Target: 128
• Locations: 4 countries
• Sites: 20

Brief Summary

Two Phase 1 studies have been conducted with AEG33773 and available safety and tolerability data from these studies support further clinical development of AEG33773. The current study is proposed as a proof-of-concept study to assess the potential analgesic efficacy of AEG33773 to reduce pain associated with chronic Diabetic Peripheral Neuropathy.

Conditions

Diabetic Peripheral Neuropathy; Chronic Pain

Keywords

Diabetic; peripheral; neuropathy; pain; hyperalgesia; allodynia

Outcome Measures

Primary Outcomes (1)

• To evaluate the potential efficacy of AEG33773 in reducing chronic pain due to DPN

  1 year

Secondary Outcomes (5)

• To evaluate a range of AEG33773 doses that provide efficacy

  1 year

• To determine a minimally effective dose of AEG33773

  1 year

• To determine a maximally tolerated dose of AEG33773

  1 year

• To evaluate the safety and tolerability of AEG33773

  1 year

• To explore AEG33773-dependent pharmacodynamic (PD) effects in blood of patients

  1 year

Study Arms (4)

Placebo

PLACEBO COMPARATOR

4 Capsules of Placebo

Drug: AEG33773 oral dosing

100 mg

ACTIVE COMPARATOR

One 100 mg capsule and 3 placebo capsules of AEG33773

Drug: AEG33773 oral dosing

200 mg

ACTIVE COMPARATOR

Two 100 mg capsules and two placebo capsules

Drug: AEG33773 oral dosing

400 mg

ACTIVE COMPARATOR

Four 100 mg AEG33773 capsules

Drug: AEG33773 oral dosing

Interventions

AEG33773 oral dosing DRUG

AEG33773 capsules: subjects will receive a daily dose of either 100 mg, 200 mg, or 400 mg AEG33773. Placebo capsules: subjects will receive a daily dose of placebo (matching test product). Capsules will be taken by mouth, over 28 consecutive days

100 mg; 200 mg; 400 mg; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female age 18 to 75 years
• Patients with type 1 or type 2 diabetes mellitus
• DPN as determined by the investigator based on clinical history, clinical examination, and assessment of signs and symptoms
• Stable diabetic control over the preceding 3 months, as determined by the investigator based on available medical information (e.g., hemoglobin A1c \[HbA1c\] and/or blood glucose levels)
• HbA1c ≤ 12 % at the Screening visit
• Pain persisting for more than 3 months and less than 5 years
• Completion of 3 daily pain intensity reports (using the 11-point NPRS) over the 3 days immediately preceding the day of randomization
• Pain intensity (NPRS) score of ≥ 5 for all 3 of the 3 days immediately preceding the day of randomization
• Completed a washout (before first NPRS assessment) of at least 7 days for any of the following medications: α2-δ antagonists (e.g., gabapentin, pregabalin), opiate analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), topical lidocaine, anti-epileptic drugs, serotonin and norepinephrine reuptake inhibitors (SNRIs) (e.g., duloxetine), tricyclic antidepressants prescribed for pain, skeletal muscle relaxants, orally administered steroids, capsaicin, mexiletene, centrally acting analgesics (dextromethorphan, tramadol), alpha lipoic acid, and any supplement or herbal product used to treat DPN symptoms
• Women must be neither pregnant nor lactating. Women of childbearing age must have a confirmed negative pregnancy test and must practice medically acceptable methods of contraception throughout the trial and for at least 30 days after the last dose of study drug
• Male subjects and/or their female partners must be using medically acceptable methods of contraception for the entire duration of the study, and for at least 90 days after the last study drug dose
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study
• A willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

You may not qualify if:

• Age younger than 18 years or older than 75 years
• Are pregnant or breast feeding
• Female patients of childbearing potential unwilling to use a medically acceptable form of contraception (i.e., hormonal birth control, intrauterine device \[IUD\], double barrier \[male condom or female condom with a diaphragm\], or a barrier method plus a spermicidal agent \[contraceptive foam, jelly, or cream\]) Female patients are considered to be of childbearing potential unless they have been postmenopausal for at least 1 year, are biologically sterile, or are surgically sterile (history of hysterectomy, bilateral oophorectomy, or bilateral tubal ligation.
• Male patients (and/or their female partners) unwilling to use a medically acceptable form of contraception during participation in the study and for at least 90 days after the last dose of study drug. Medically acceptable forms of contraception are hormonal birth control, intrauterine device (IUD), double barrier (male condom or female condom with a diaphragm), or a barrier method plus a spermicidal agent (contraceptive foam, jelly, or cream)
• Treatment with local anesthetic nerve blocks within the last 30 days before the Screening visit
• Other severe pain which may impair the self-assessment of pain due to DPN
• Participation in another study within 30 days before the Screening visit and/or during study participation
• History of drug or alcohol abuse within the past 2 years
• Creatinine clearance \< 50 mL/min at the Screening visit
• Malignancy other than basal cell carcinoma and carcinoma in situ within the past 2 years
• History of chronic hepatitis B or C, hepatitis within the past 3 months before the Screening visit, or any history of human immunodeficiency virus (HIV) infection
• Clinically significant hepatic, respiratory, hematological, cardiovascular, renal, or neurological disease, with the exception of diabetic peripheral neuropathy
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times higher than the upper limit of the laboratory normal reference range at the Screening visit
• Immunocompromised state
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation

Sponsors & Collaborators

• Aegera Therapeutics: lead

Study Sites (20)

Neurological Research Institute

Santa Monica, California, 90404, United States

Location

Radiant Research

Cincinnatti, Ohio, 45249, United States

Location

Wells Institute for Health Awareness

Kettering, Ohio, 45429, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Multiprofile Hospital for Active Treatment - Internal Department

Byala, 7100, Bulgaria

Location

University Multiprofile Hospital for Active Treatment - Clinic of Endocrinology and Metabolic Diseases

Pleven, 5800, Bulgaria

Location

University Multiprofile Hospital for Active Treatment - Clinic of Endocrinology and Metabolic Diseases

Plovdiv, 4002, Bulgaria

Location

Multiprofile Hospital for Active Treatment - Therapeutical and Endocrinology Department

Rousse, 7002, Bulgaria

Location

University Multiprofile Hospital Treatment Stara Zagora

Stara Zagora, 6003, Bulgaria

Location

Clinique d'Endocrinologie de l'Outaouais

Hull, Quebec, J8V 2P5, Canada

Location

Centre de Recherche Clinique de Laval

Laval, Quebec, H7T 2P5, Canada

Location

Hopital de l'Enfant Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

Medical Center "Dr. Negrisanu" SRL

Timișoara, Transylvania, 300456, Romania

Location

S.C. Nicodiab SRL

Bucharest, 010496, Romania

Location

National Clinical Institute of Diabetes, Nutrition and Metabolic Diseases

Bucharest, 020045, Romania

Location

National Institute of Diabetes Nutrition and Metabolic Diseases

Bucharest, 020475, Romania

Location

Mosilor Diabetes Mellitus and Obesity Medical

Bucharest, 020859, Romania

Location

Emergency Clinical County Hospital Cluj County

Cluj-Napoca, 4000006, Romania

Location

St. Spiridon Emergency Clinical County Hospital

Iași, 700111, Romania

Location

MeSH Terms

Conditions

Chronic Pain; Pain; Hyperalgesia

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Somatosensory Disorders; Sensation Disorders; Nervous System Diseases

Study Officials

• Jacques Jolivet, MD, FRCP(C)

  Aegera Therapeutics, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 30, 2009
• First Posted: May 1, 2009
• Study Start: March 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: February 1, 2010
• Last Updated: May 31, 2010

Record last verified: 2010-05

Locations

CA (3); US (5); BU (5); RO (7)