Safety, Tolerability, and Efficacy of IA Verapamil in the Treatment of Joint Pain in Subjects With Osteoarthritis of the Knee

NCT01645709 | Terminated Phase 1 Results

• 1 other identifier: CS-201
• Study Type: interventional
• Target: 81
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, double-blind, placebo-controlled, multi-center study to evaluate the safety, tolerability, and efficacy of Intra-Articular (IA) verapamil in the treatment of joint pain in patients with knee osteoarthritis (OA). Subjects will discontinue all analgesic medications for the entire duration of the study, except for acetaminophen (taken on an as needed basis at no more than 2 g/day). At visit 2, subjects who meet all entry criteria will be randomized to receive a single injection of IA verapamil or IA placebo at a ratio of 1:1. Treatments will be given with fluoroscopy or ultrasound to confirm needle placement. Subjects will be monitored for blood pressure and heart rate (sitting and standing) for at least 1 hour post-injection. Subjects will be evaluated at weeks 1, 2, 3, 4, 6, 8, and 12 after treatment.

Conditions

Osteoarthritis of the Knee

Outcome Measures

Primary Outcomes (1)

• Compare Efficacy of Verapmil vs Placebo at Week 4

  To compare the efficacy of IA verapamil versus IA placebo for pain relief using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at week 4.

  4 weeks

Secondary Outcomes (8)

• Compare Efficacy of Verapamil to Placebo Compared to Baseline

  13 weeks

• Compare Efficacy of Verapamil to Placebo Compared to Baseline

  13 weeks

• Compare Efficacy of Verapamil to Placebo Compared to Baseline

  13 weeks

• Compare Efficacy of Verapamil to Placebo Compared to Baseline

  13 weeks

• Compare Efficacy of Verapamil to Placebo Compared to Baseline

  13 weeks

Study Arms (2)

Verapamil

EXPERIMENTAL

Subjects will be randomized to receive a single injection of IA Verapamil or IA Placebo at a ratio of 1:1.

Drug: Verapamil

Placebo

PLACEBO COMPARATOR

Subjects will be randomized to receive a single injection of IA Verapamil or IA Placebo at a ratio of 1:1.

Drug: Placebo

Interventions

Verapamil DRUG

Verapamil

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be 35-75 years of age and in good general medical and psychological health.
• Be able to speak, read, write, and understand English, understand the consent form, complete study-related procedures, and communicate with the study staff.
• Have OA of at least 1 knee (target knee) for at least 6 months and meet all the following criteria:
• OA documented by standing X-rays anterior-posterior patella-femoral view taken within 1 month of screening visit indicating Kellgren-Lawrence Grade 2 to early-stage Grade 4 radiographic stage of the knee;
• Have pain associated with OA of the target knee for at least 25 of the last 30 days; c. Meet the American College of Rheumatology clinical classification criteria, defined as having pain in the target knee and at least 3 of the following 6 items:
• Age \> 50;
• Morning stiffness \<30 minutes;
• Crepitus on active motion;
• Bony tenderness;
• Bony enlargement;
• No palpable warmth of synovium.
• Target knee does not have any type of orthopedic and/or prosthetic device.
• Based on standard physical examination of the target knee, does not have any neurovascular deficits, any skin abnormalities, any meniscal abnormalities, or any ligament instability.
• At treatment visit 2 prior to randomization, have a score of at least 20 on the WOMAC pain subscale (questions 1-5) for the target knee and an in-clinic average pain intensity score of at least 4/10 on the 0-10 NRS for the 24-hour recall.
• Be willing to maintain any present stable treatment modalities (e.g., acupuncture or physical therapy) and be willing to refrain from initiating any new treatment modalities.

You may not qualify if:

• Subjects who meet any of the following criteria will not be eligible to participate:
• Have a Kellgren-Lawrence Grade 1 radiographic stage of the knee or have Kellgren-Lawrence Grade 4 radiographic end stage of the knee with bone on bone, ie, less than 2 mm joint space.
• Be a candidate for knee replacement within next 6 months.
• Have a body mass index \> 35 kg/m2.
• Have a Hospital Anxiety and Depression Scale score \>12 on either subscale or have an established history of major depressive disorder not controlled with medication.
• Have, in the Investigator's opinion, clinically significant abnormalities in clinical laboratory tests (hematology, clinical labs, urinalysis).
• Have a positive urine drug test for illegal drug substances at screening.
• Have, in the Investigator's opinion, clinically significant abnormalities in electrocardiogram readings
• If a female of childbearing potential, have a positive pregnancy test at screening.
• Have significant pain outside the target knee, including significant hip or back pain (bilateral knee OA will be allowed as long as target knee pain can be distinguished from contralateral knee pain and contralateral knee does not require treatment).
• Have pain affecting the target knee that is due to any etiology other than OA.
• Have documented history of inflammatory arthritis, including rheumatoid arthritis.
• Have a meniscal tear in the target knee.
• Have had viscosupplementation with hyaluronic acid products within 6 months prior to screening.
• Have failed to respond to prior treatment with viscosupplementation with hyaluronic acid products.

Sponsors & Collaborators

• Calosyn Pharma, Inc.: lead
• Premier Research: collaborator

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Verapamil

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Stephen Snowdy, PhD
• Organization: CaloSyn Pharma Inc.

ssnowdy@ansleyvc.com

404-863-8892

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2012
• First Posted: July 20, 2012
• Study Start: April 1, 2012
• Primary Completion: February 1, 2013
• Last Updated: September 5, 2014
• Results First Posted: September 5, 2014

Record last verified: 2014-08