Trial record 5 of 7 for:    topical gels AND transdermal

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2015 by Transdermal Therapeutics, Inc.
Sponsor:
Collaborators:
Albert Einstein College of Medicine of Yeshiva University
Montefiore Medical Center
Information provided by (Responsible Party):
Transdermal Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02485145
First received: June 17, 2015
Last updated: June 25, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Osteoarthritis of the Hands
Drug: A/B
Drug: Placebo
Drug: B/A
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: The Analgesic Activity of a Topical Formulation in Patients With Osteoarthritis of the Hands

Resource links provided by NLM:


Further study details as provided by Transdermal Therapeutics, Inc.:

Primary Outcome Measures:
  • 100 mm Visual Analog Scale [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Measurement of OA pain intensity

  • Australia/Canadian Osteoarthritis Index [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Measurement of osteoarthritis hand function

  • 100 mm Visual Analog Scale [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Global rating of disease activity

  • Composite Pharmacokinetics [ Time Frame: Blood will be drawn at study day 7, study day 14, study day 21, and study day 28 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Use of rescue medication [ Time Frame: The entire 28 day study ] [ Designated as safety issue: No ]
    Acetaminophen up to 4 grams daily.


Estimated Enrollment: 40
Study Start Date: July 2015
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A/B
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
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.
Other Names:
  • Diclofenac 3%
  • Baclofen 2%
  • Orphenadrine 5%
  • Bupivacaine 2%
  • VersaPro cream
Drug: Placebo
The placebo, which consists of the VersaPro cream, will be utilized in the study.
Other Name: VersaPro cream
Experimental: B/A
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
The placebo, which consists of the VersaPro cream, will be utilized in the study.
Other Name: VersaPro cream
Drug: B/A
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.
Other Names:
  • Diclofenac 3%
  • Baclofen 2%
  • Orphenadrine 5%
  • Bupivacaine 2%
  • VersaPro cream

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.

  Eligibility

Ages Eligible for Study:   40 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT02485145

Contacts
Contact: Ann Ribe, B.A. 205-917-5432 annribe@transdermalinc.com
Contact: John Hardin, M.D. 917-331-5641 jhardin@montefiore.org

Sponsors and Collaborators
Transdermal Therapeutics, Inc.
Albert Einstein College of Medicine of Yeshiva University
Montefiore Medical Center
Investigators
Principal Investigator: John Hardin, M.D. Albert Einstein College of Medicine - Yeshiva University and Montefiore Medical Center
  More Information

No publications provided

Responsible Party: Transdermal Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02485145     History of Changes
Other Study ID Numbers: 54321
Study First Received: June 17, 2015
Last Updated: June 25, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Federal Government

Keywords provided by Transdermal Therapeutics, Inc.:
Topical
Hand osteoarthritis

Additional relevant MeSH terms:
Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Bupivacaine
Diclofenac
Orphenadrine
Analgesics
Analgesics, Non-Narcotic
Anesthetics
Anesthetics, Local
Anti-Dyskinesia Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antiparkinson Agents
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Cholinergic Agents
Cholinergic Antagonists
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Muscle Relaxants, Central
Neuromuscular Agents
Neurotransmitter Agents
Parasympatholytics

ClinicalTrials.gov processed this record on June 30, 2015