Pharmacokinetics, Bioavailability and Safety of PENNSAID® Gel

NCT01202799 | Completed Phase 1

• 1 other identifier: COV05100070
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

It is anticipated that PENNSAID Gel will minimize systemic exposure versus oral diclofenac administered twice a day (BID). In addition, PENNSAID Gel should result in greater subject convenience and compliance with a comparable bioavailability, safety and tolerability profile to that of the approved PENNSAID solution administered four times a day (QID).

Conditions

Pain

Keywords

Pharmacokinetics; Healthy volunteers; PENNSAID; Topical NSAID; Diclofenac

Outcome Measures

Primary Outcomes (1)

• The rate and extent of exposure of diclofenac will be assessed.

  Summary statistics including the mean, standard deviation, coefficient of variation, geometric mean and geometric %CV will be calculated for all PK parameters by treatment.

  During each of the 3 periods, blood samples will be obtained on Day 1 and Day 8 at pre-dose and 1, 2, 3, 4, 6, 8 and 12 hours post-dose; on Days 2-7 at pre-dose; and on Days 9, 13 and 15 at approximately 8 AM.

Study Arms (3)

Treatment A

EXPERIMENTAL

2% w/w diclofenac sodium topical gel

Drug: 2% w/w diclofenac sodium topical gel

Treatment B

ACTIVE COMPARATOR

Drug: 1.5% w/w diclofenac sodium topical solution

Treatment C

ACTIVE COMPARATOR

Drug: 75 mg diclofenac sodium delayed release tablet

Interventions

2% w/w diclofenac sodium topical gel DRUG

2% w/w diclofenac sodium topical gel

Treatment A

1.5% w/w diclofenac sodium topical solution DRUG

1.5% w/w diclofenac sodium topical solution

Treatment B

75 mg diclofenac sodium delayed release tablet DRUG

75 mg diclofenac sodium delayed release tablet

Treatment C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed and dated IRB approved consent before any protocol procedures are performed.
• Males or non-pregnant, non-lactating females, minimum 18 years of age and maximum of 55 years of age.
• Female subjects must be negative on a serum pregnancy test, be postmenopausal for at least 1 year, surgically sterile, or using an acceptable form of contraception for 30 days prior to dosing and for the duration of study participation.
• Subjects with a body mass index (BMI) ≥19 and ≤29 kg/m².
• The findings from the ECG interpretation must be within the normal range.
• Subjects whose health status is assessed by the investigator as "normal healthy" by required screening and check-in assessments.
• Subjects must be able to provide written consent and agree to comply with study requirements.

You may not qualify if:

• Subjects will be ineligible for the study if they meet any of the following criteria:
• Known hypersensitivity to diclofenac, aspirin \[acetylsalicylic acid (ASA)\] or any other NSAID, dimethyl sulfoxide (DMSO) or ethanol. This includes subjects exhibiting aspirin or other NSAID-induced symptoms, including bronchospasm, rhinitis, and urticaria or other NSAID-induced allergic symptoms.
• Pregnant or lactating women. Women of reproductive potential (and women \<12 months after menopause) may not participate unless they have agreed to use an effective contraceptive method while on study.
• Evidence of any serious active infections, severe uncontrolled cardiac, renal, hepatic, pulmonary or other systemic disease, significant medical or psychiatric illness, known seropositivity to HIV, known unexplained vision changes, history of unexplained syncope, lightheadedness, high blood pressure, chronic hepatic conditions like hepatic porphyria or clinically significant laboratory findings that would, in the investigators judgment, make the subject inappropriate for the study.
• Documented (upper GI series or endoscopy) gastroduodenal ulcer or any GI bleeding (except hemorrhoidal) within the last 6 months prior to screening.
• Abnormal hepatic and renal functions; hematologic changes:
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)≥2.5 X ULN
• Gamma-glutamyl transpeptidase (GGT) ≥3X ULN
• Total bilirubin ≥1.5X ULN
• Serum creatinine ≥1.5X ULN
• Hemoglobin ≤LLN.
• Major surgery or previous damage to the study knee(s) at any time (eg. total knee replacement, damage/reconstruction of the anterior or posterior cruciate ligaments), or minor knee surgery (eg, cartilage repair, collateral ligament repair, arthroscopic debridement) to the study knee(s) within 1 year prior to screening.
• Administration of a sedative hypnotic medication for insomnia within 14 days prior to screening.
• Administration of anti-depressants, within 60 days prior to screening.
• Administration of another investigational drug within the previous 30 days prior to screening.

Sponsors & Collaborators

• Mallinckrodt: lead

Study Sites (1)

Comprehensive Phase One

Miramar, Florida, 33025, United States

Location

Related Publications (1)

• Holt RJ, Taiwo T, Kent JD. Bioequivalence of diclofenac sodium 2% and 1.5% topical solutions relative to oral diclofenac sodium in healthy volunteers. Postgrad Med. 2015 Aug;127(6):581-90. doi: 10.1080/00325481.2015.1058689. Epub 2015 Jun 16.

  PMID: 26077436 DERIVED

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Maria J Gutierrez, MD

  Comprehensive Phase One ®

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2010
• First Posted: September 16, 2010
• Study Start: September 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: September 23, 2014

Record last verified: 2014-09

Locations

US (1)