The Analgesic Activity of a Topical Formulation in Patients With Osteoarthritis of the Hands

NCT02485145 | Unknown Early Phase 1 DMC

• 1 other identifier: 54321
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

Osteoarthritis (OA) affects over 30 million people in the United States and represents our nation's leading cause of disability. Data for the years between 1996-2005, indicate that OA raised overall health care costs by $185.5 billion annually. Largely as a consequence of this disease, the number of patients undergoing joint replacement surgery will quadruple over the next 17 years. Importantly, several recent studies have demonstrated that OA is an independent risk factor for cardiovascular disease . Presently investigators have no medications that alter the natural history of OA. Weight control, exercise and some physical therapy measures are the only interventions short of total joint replacement that alter the course of this disease. To make matters worse, investigators have experienced only setbacks in use of medications aimed at symptom control. Recognition of toxicities of non-steroidal anti-inflammatory drugs (NSAIDs) and narcotic-based analgesics has narrowed the presently available armamentarium for pain control in OA . Clearly OA is a major factor that demands better solutions as the health care system is redesigned. OA involving the hands represents a major part of the overall burden of this disease. In radiographic surveys about a quarter of the total US population has changes consistent with OA involving the hands. Among the elderly, radiographic hand OA has been found in over half of such individuals and as many as a quarter of them suffer from pain and functional incapacitation. The joints affected typically are the first carpometacarpal (CMC-1) joint, the distal interphalangeal (DIP) joints, and the proximal interphalangeal (PIP) joints . Therapeutic options include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and a variety of physical measures such as physical therapy, bracing, and heat and cold applications. To achieve some symptomatic benefit while limiting systemic toxicity, topical therapies have been developed which either act as counter irritants, seek to reduce substance P (capsaicin), or to deliver an NSAID locally through the skin. The leading example of the latter is Diclofenac sodium gel which was shown to reduce pain intensity and improve hand function in a double blind controlled trial. However none of these measures have proven sufficiently effective to meet patient needs. Topical polytherapy will be employed in this study to see if it will be effective against the pain of OA.

Conditions

Osteoarthritis of the Hands

Keywords

Topical; Hand osteoarthritis

Outcome Measures

Primary Outcomes (4)

• 100 mm Visual Analog Scale

  Measurement of OA pain intensity

  Participants will be followed for the 28 days of the study length, with the study measure being given at study day 7, study day 14, study day 21 and study day 28.

• Australia/Canadian Osteoarthritis Index

  Measurement of osteoarthritis hand function

  Participants will be followed for the 28 days of the study length, with the study measure being given at study day 7, study day 14, study day 21 and study day 28.

• 100 mm Visual Analog Scale

  Global rating of disease activity

  Participants will be followed for the 28 days of the study length, with the study measure being given at study day 7, study day 14, study day 21 and study day 28.

• Composite Pharmacokinetics

  Participants will be followed for the 28 days of the study length, with the pharmacokinetics being tested at study day 7, study day 14, study day 21 and study day 28 to see the systemic absorption of each of the study drugs. Each drug (Diclofenac, Baclofen, Orphenadrine and Bupivacaine) will be tested for Peak Plasma Concentration (C max) and the area under the plasma concentration versus time curve (AUC).

  Blood will be drawn at study day 7, study day 14, study day 21, and study day 28

Secondary Outcomes (1)

• Use of rescue medication

  The entire 28 day study

Study Arms (2)

A/B

EXPERIMENTAL

In this crossover trial, the A/B group will receive the test product (A) and then the placebo (B). The topical product contains the following: Diclofenac 3%, Baclofen 2%, Orphenadrine Citrate 5% and Bupivacaine 2% in a VersaPro cream, while the placebo is the VersaPro cream alone. Participants will use the test product for 7 days, applying the topical product to the hands twice a day. There will be a 7 day washout period, and then participants will be given the placebo cream, which will be used for 7 days, applying the topical placebo to the hands twice a day.

Drug: A/B; Drug: Placebo

B/A

EXPERIMENTAL

In this crossover trial, the B/A group will receive the placebo (B) and then the test product (A). The product contains the following: Diclofenac 3%, Baclofen 2%, Orphenadrine Citrate 5% and Bupivacaine 2% in a VersaPro cream, while the placebo is the VersaPro cream alone. Participants will use the placebo product for 7 days, applying the placebo product to the hands twice a day. There will be a 7 day washout period, and then participants will be given the test cream, which will be used for 7 days, applying the topical product to the hands twice a day.

Drug: Placebo; Drug: B/A

Interventions

A/B DRUG

This arm uses the test product first, which consists of Diclofenac 3%, Baclofen 2%, Orphenadrine 5%, and Bupivacaine 2% in a VersaPro cream. This is the A arm. The B arm is the second arm, and consists of the VersaPro cream alone.

Also known as: Diclofenac 3%, Baclofen 2%, Orphenadrine 5%, Bupivacaine 2%, VersaPro cream

A/B

Placebo DRUG

The placebo, which consists of the VersaPro cream, will be utilized in the study.

Also known as: VersaPro cream

A/B; B/A

B/A DRUG

This arm uses the placebo product first, which consists of the VersaPro cream alone. This is the B arm. The A arm is the second arm, which consists of the test product which consists of Diclofenac 3%, Baclofen 2%, Orphenadrine 5%, and Bupivacaine 2% in a VersaPro cream. This is the A arm.

Also known as: Diclofenac 3%, Baclofen 2%, Orphenadrine 5%, Bupivacaine 2%, VersaPro cream

B/A

Eligibility Criteria

• Age: 40 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• OA in at least one hand as defined by ACR Criteria (nodal enlargement in two or more of 10 defined joints, CMC-1, MCP=1, PIPs and DIPs).
• Hand pain duration greater than one year.
• History of NSAID use for hand pain on at least one occasion during the last year.
• Age 40 to 79 years.
• Ability to understand the English language and to comprehend written material at the 5th grade level.

You may not qualify if:

• History of psoriasis
• Other painful rheumatic disease, measured by a blood draw that will test for RF factor and ESR.
• Rheumatoid arthritis, as measured by hand x-rays.
• Any diagnosis of fibromyalgia or neurovascular disease.
• Presence of Raynaud's disease.
• Presence of Raynaud's disease.
• Presence of any peripheral neuropathy.
• Presence of cervical radiculopathy.
• Pregnancy in females (pregnancy test will be administered at intake to females of reproductive capability and their method of birth control recorded.)
• Persons under age 40. Insufficient data are available in adults to judge potential risk in children.
• Those who are not capable of providing informed consent.
• Known allergy to analgesic drugs and the drugs used in this study.
• Those who do not comprehend English. As this is a short-term Pilot study, the potential benefits to the participants is currently unknown. Based upon this knowledge, we believe we are exempt from the requirement to translate the informed consent form into Spanish.
• Those with renal and/or gastrointestinal impairments, i.e. with a creatinine level of 2 and GFS level 4.

Sponsors & Collaborators

• Transdermal Therapeutics, Inc.: lead
• Albert Einstein College of Medicine: collaborator
• Montefiore Medical Center: collaborator

MeSH Terms

Interventions

Bupivacaine

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• John Hardin, M.D.

  Albert Einstein College of Medicine - Yeshiva University and Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ann Ribe, B.A.

CONTACT

205-917-5432; annribe@transdermalinc.com

John Hardin, M.D.

CONTACT

917-331-5641; jhardin@montefiore.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2015
• First Posted: June 30, 2015
• Study Start: July 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: March 1, 2016
• Last Updated: June 30, 2015

Record last verified: 2015-06