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

This study has been completed.
Sponsor:
Information provided by:
Aegera Therapeutics
ClinicalTrials.gov Identifier:
NCT00891683
First received: April 30, 2009
Last updated: May 28, 2010
Last verified: May 2010
  Purpose

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.


Condition Intervention Phase
Diabetic Peripheral Neuropathy
Chronic Pain
Drug: AEG33773 oral dosing
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Safety and Efficacy of AEG33773 Versus Placebo in Patients With Painful Diabetic Peripheral Neuropathy

Resource links provided by NLM:


Further study details as provided by Aegera Therapeutics:

Primary Outcome Measures:
  • To evaluate the potential efficacy of AEG33773 in reducing chronic pain due to DPN [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate a range of AEG33773 doses that provide efficacy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To determine a minimally effective dose of AEG33773 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To determine a maximally tolerated dose of AEG33773 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To evaluate the safety and tolerability of AEG33773 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • To explore AEG33773-dependent pharmacodynamic (PD) effects in blood of patients [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 128
Study Start Date: March 2009
Study Completion Date: February 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
4 Capsules of Placebo
Drug: AEG33773 oral dosing
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
Active Comparator: 100 mg
One 100 mg capsule and 3 placebo capsules of AEG33773
Drug: AEG33773 oral dosing
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
Active Comparator: 200 mg
Two 100 mg capsules and two placebo capsules
Drug: AEG33773 oral dosing
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
Active Comparator: 400 mg
Four 100 mg AEG33773 capsules
Drug: AEG33773 oral dosing
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

Detailed Description:

Doses of AEG33773 selected for evaluation in this study provide a dose range (i.e., 100-400 mg) that may potentially include both a minimally effective dose and a maximum tolerated dose. Doses up to 400 mg were well tolerated in single- and multiple-dose Phase 1 studies.

Before initiation of treatment with study drug, other analgesic medications will be discontinued during a 7-day Washout Period, and neuropathic pain will be assessed (in the absence of analgesic medication) over the next 3 days (Pain Assessment Period). Pain intensity level during these 3 days will be recorded daily, and only those subjects who meet predefined pain intensity threshold criteria on all 3 days will be eligible to receive study drug. Because pain may increase after analgesic medications have been discontinued, the combined length of the Washout and Pain Assessment Periods is limited in order that subjects who experience increased pain during this time may begin treatment with study drug without undue delay. This design will allow for adequate Baseline pain assessment over 3 days while avoiding a more prolonged period of increasing pain in the absence of analgesic medications.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • ECG with a QTcB > 470 ms at the Screening visit or at Baseline (if at either the Screening visit or Baseline the ECG shows a QTcB > 470 ms, then the investigator may immediately repeat the ECG twice and the QTcB value for inclusion/exclusion purposes will be determined by calculating the average of the 3 readings)
  • Immunocompromised state
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00891683

Locations
United States, California
Neurological Research Institute
Santa Monica, California, United States, 90404
United States, Ohio
Radiant Research
Cincinnatti, Ohio, United States, 45249
Wells Institute for Health Awareness
Kettering, Ohio, United States, 45429
United States, Pennsylvania
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Bulgaria
Multiprofile Hospital for Active Treatment - Internal Department
Byala, Bulgaria, 7100
University Multiprofile Hospital for Active Treatment - Clinic of Endocrinology and Metabolic Diseases
Pleven, Bulgaria, 5800
University Multiprofile Hospital for Active Treatment - Clinic of Endocrinology and Metabolic Diseases
Plovdiv, Bulgaria, 4002
Multiprofile Hospital for Active Treatment - Therapeutical and Endocrinology Department
Ruse, Bulgaria, 7002
University Multiprofile Hospital Treatment Stara Zagora
Stara Zagora, Bulgaria, 6003
Canada, Quebec
Clinique d'Endocrinologie de l'Outaouais
Hull, Quebec, Canada, J8V 2P5
Centre de Recherche Clinique de Laval
Laval, Quebec, Canada, H7T 2P5
Canada
Hopital de l'Enfant Jesus
Quebec, Canada, G1J 1Z4
Romania
Medical Center "Dr. Negrisanu" SRL
Timisoara, Transylvania, Romania, 300456
National Institute of Diabetes Nutrition and Metabolic Diseases
Bucharest, Romania, 020475
National Clinical Institute of Diabetes, Nutrition and Metabolic Diseases
Bucharest, Romania, 020045
S.C. Nicodiab SRL
Bucharest, Romania, 010496
Mosilor Diabetes Mellitus and Obesity Medical
Bucharest, Romania, 020859
Emergency Clinical County Hospital Cluj County
Cluj Napoca, Romania, 4000006
St. Spiridon Emergency Clinical County Hospital
Iasi, Romania, 700111
Sponsors and Collaborators
Aegera Therapeutics
Investigators
Study Director: Jacques Jolivet, MD, FRCP(C) Aegera Therapeutics, Inc
  More Information

No publications provided

Responsible Party: Jacques Jolivet, MD, Senior VP Clinical, Aegera Therapeutics Inc
ClinicalTrials.gov Identifier: NCT00891683     History of Changes
Other Study ID Numbers: AEG33773-201
Study First Received: April 30, 2009
Last Updated: May 28, 2010
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Bulgaria: Bulgarian Drug Agency
Romania: Ministry of Public Health
Romania: National Medicines Agency

Keywords provided by Aegera Therapeutics:
Diabetic
peripheral
neuropathy
pain
hyperalgesia
allodynia

Additional relevant MeSH terms:
Peripheral Nervous System Diseases
Chronic Pain
Diabetic Neuropathies
Neuromuscular Diseases
Nervous System Diseases
Pain
Neurologic Manifestations
Signs and Symptoms
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases

ClinicalTrials.gov processed this record on August 18, 2014