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

Condition(s) targeted: Osteoarthritis of the Hands

Intervention: A/B (Drug); Placebo (Drug); B/A (Drug)

Phase: Phase 0

Status: Not yet recruiting

Sponsored by: Transdermal Therapeutics, Inc.

Official(s) and/or principal investigator(s):
John Hardin, M.D., Principal Investigator, Affiliation: Albert Einstein College of Medicine - Yeshiva University and Montefiore Medical Center

Overall contact:
Ann Ribe, B.A., Phone: 205-917-5432, Email: annribe@transdermalinc.com

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome:

100 mm Visual Analog Scale

Australia/Canadian Osteoarthritis Index

100 mm Visual Analog Scale

Composite Pharmacokinetics

Secondary outcome: Use of rescue medication

Detailed description: A potentially more effective approach is to provide a combination of analgesic and anti-inflammatory agents through a topical delivery system. In the present study compounds with anti-inflammatory and analgesic properties will be combined in a vehicle that promotes penetration of molecules through the skin to deeper underlying tissues such as the joint capsule at articulations in the hands. The vehicle consists of Versapro cream base (a formulation of Medisca, Inc. that contains Vitamin E and Aloe Vera, along with other ingredients that are proprietary), Tranilast powder, Pentoxifylline USP powder, Cetyl Myristoleate 40% wax, liquid Pentylene Glycol, liquid Dimethyl Sulfoxide (DMSO) USP, liquid Propylene Glycol USP, liquid Ethoxy Diglycol reagent, liquid Ethyl Alcohol 190 proof USP. These are all inert ingredients, i. e. they only promote penetration of molecules through the skin. A mixture of the following compounds will be incorporated into this vehicle as the active test medication:

Diclofenac 3% - an NSAID. FDA pregnancy category C for the first 30 weeks, then category D.

Baclofen 2% - an agonist for the GABAB receptors. FDA pregnancy category C.

Orphenadrine 5% - an anticholinergic drug of the ethanolamine antihistamine class. FDA

pregnancy category C.

Bupivacaine 2% - a local anesthetic that binds voltage-gated sodium channels and blocks

sodium influx into nerve cells preventing depolarization. FDA pregnancy category C. Due to the FDA pregnancy categories for the drugs used in this study, pregnancy is an exclusion criteria. The control medication: The vehicle alone will serve as the control compound.

Minimum age: 40 Years. Maximum age: 79 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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. Exclusion Criteria:

- 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.

Ann Ribe, B.A., Phone: 205-917-5432, Email: annribe@transdermalinc.com

Starting date: July 2015
Last updated: June 25, 2015