Pharmacokinetics, Bioavailability and Safety of PENNSAID� Gel
Information source: Mallinckrodt
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pain
Intervention: 2% w/w diclofenac sodium topical gel (Drug); 1.5% w/w diclofenac sodium topical solution (Drug); 75 mg diclofenac sodium delayed release tablet (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Mallinckrodt Official(s) and/or principal investigator(s): Maria J Gutierrez, MD, Principal Investigator, Affiliation: Comprehensive Phase One ®
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).
Clinical Details
Official title: A Phase 1, Randomized, Single Center, Open-Label, Multiple-Dose, Three-Way Crossover Study to Evaluate the Pharmacokinetics, Bioavailability and Safety of PENNSAID Gel in Comparison With Sandoz 75 mg Diclofenac Sodium Delayed Release Tablet and PENNSAID (Diclofenac Sodium Topical Solution) in Healthy Volunteers
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: The rate and extent of exposure of diclofenac will be assessed.
Detailed description:
PENNSAID Gel is a new topical gel formulation of diclofenac sodium that is similar in
composition to PENNSAID solution.
No clinical studies have been conducted using PENNSAID Gel. The current study will compare
the pharmacokinetics, bioavailability, safety and tolerability of diclofenac after the
topical application of PENNSAID Gel with the approved formulations of topical PENNSAID
Solution and oral Sandoz 75 mg diclofenac sodium delayed release tablets in healthy
subjects.
The efficacy profile of PENNSAID Gel is based on the known efficacy profile of PENNSAID
solution. Support for the BID dosing regimen includes the higher concentration of diclofenac
sodium in PENNSAID Gel (2. 0%) compared to PENNSAID solution (1. 5%). In addition, compared to
PENNSAID solution, PENNSAID Gel is designed to have better penetration of diclofenac to
allow for a reduction in the number of applications per day from four to two while
maintaining effectiveness.
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- The eligibility of subjects to enter the study is based on meeting the inclusion
criteria listed below:
1. Signed and dated IRB approved consent before any protocol procedures are
performed.
2. Males or non-pregnant, non-lactating females, minimum 18 years of age and
maximum of 55 years of age.
3. 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.
4. Subjects with a body mass index (BMI) ≥19 and ≤29 kg/m².
5. The findings from the ECG interpretation must be within the normal range.
6. Subjects whose health status is assessed by the investigator as "normal healthy"
by required screening and check-in assessments.
7. Subjects must be able to provide written consent and agree to comply with study
requirements.
Exclusion Criteria:
- Subjects will be ineligible for the study if they meet any of the following criteria:
1. 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.
2. 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.
3. 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.
4. Documented (upper GI series or endoscopy) gastroduodenal ulcer or any GI
bleeding (except hemorrhoidal) within the last 6 months prior to screening.
5. 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.
6. 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.
7. Administration of a sedative hypnotic medication for insomnia within 14 days
prior to screening.
8. Administration of anti-depressants, within 60 days prior to screening.
9. Administration of another investigational drug within the previous 30 days prior
to screening.
10. Skin disorder that affects palms of the hands or the application site of the
knee(s).
11. History of chronic headaches.
12. Documented history of alcohol or drug abuse within 1 year prior to the screening
visit
13. Subjects who have smoked or used nicotine-containing products within 6 months
prior to Period 1 dosing.
14. Subjects treated with systemic or local diclofenac within one month of study Day
1.
15. Using artificial exposure, tanning beds, or self-tanning cream on knee area
within 90 days of study start.
16. Donation or significant loss of blood (480 mL or more) within 30 days of dosing.
17. Previous participation in this study or participation in another clinical trial
within 30 days prior screening.
18. Noncompliance with the study protocol.
Locations and Contacts
Comprehensive Phase One, Miramar, Florida 33025, United States
Additional Information
Starting date: September 2010
Last updated: September 22, 2014
|