Bioavailability and Safety Study Comparing Two Dose Levels of AMZ001 and One Dose Level of Diclofenac Sodium 1% Gel in Healthy Participants

A Phase 1, Single-Center, Randomized, Open-Label, Bioavailability and Safety Three Period Crossover Multiple-Dose Study Comparing Two Dose Levels of AMZ001 (Diclofenac Sodium Gel 3.06%) and One Dose Level of Diclofenac Sodium 1% Gel in Healthy Subjects

The goal of this clinical trial is to compare drug exposure from two different products (AMZ001 and Diclofenac Sodium 1% Gel) in healthy participants on Day 7 after repeated topical administrations for 7 days.

Participants will receive, in a crossover design, three different treatments

• AMZ001 Low dose
• AMZ001 High dose
• Diclofenac Sodium 1% Gel

Safety and tolerability of AMZ001 will be also investigated.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Diclofenac Sodium Gel

Detailed Description

On their both knees, participants will apply once daily either low dose of AMZ001 or high dose of AMZ001 for 7 consecutive days. Participants will also apply Diclofenac Sodium 1% Gel as per label information on each knee.

Intensive pharmacokinetic assessment (blood samplings) will be performed on the first day of application (Day 1) as well as on the last day of application (Day 7).

Each participant will receive each of the three treatments in a randomized manner. Between each treatment, participant will not receive any of the three tested therapies between 3 weeks before receiving the next therapy. (washout period)

Participants will stay on the clinical unit only during each period of treatment but not during washout period.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Fair Lawn, New Jersey, United States, 07410
      • TKL Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy male or female participants 18-65 years of age (e.g., in general good physical health, as judged by the Investigator and no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG (electrocardiogram) or clinical laboratory tests)
• Has a body mass index (BMI) between 18.0 and 35.0 kg/m^2 (kilogram per square meter) at Screening.
• In the case of females of child-bearing potential ([FCBP) unless surgically sterilized [hysterectomy, bilateral oophorectomy, bilateral tubal ligation] or are postmenopausal for at least 12 months), are using two acceptable forms of birth control (hormonal contraceptives i.e., oral/implant/injectable/transdermal; intrauterine device (IUD) and/or barrier methods [female condom, male condom, diaphragm, cervical cap, spermicide]; note: 2 barrier methods are two acceptable forms of birth control)). Abstinence or partner's vasectomies are acceptable if the female participant agrees to implement two acceptable forms of birth control if her lifestyle/partner changes.
• Females of child-bearing potential have a negative serum pregnancy test (SPT) at Screening and negative urine pregnancy test (UPT) on Day -1 of each period and at end of treatment (EOT) visit
• Are free of any systemic or dermatologic disorder and chronic or acute infections, which, in the opinion of the Principal Investigator (PI), will interfere with the study results or increase the risk of adverse events (AEs)
• Read, understand, and provide signed informed consent before any assessment is performed.

Exclusion Criteria:

• Participant has any visible skin disease, skin lesions, wounds, or a significant amount of hair at the application site (knee)
• Use of an investigational medicinal product (IMP) within 30 days or 5 half-lives (if known), whichever is longer, of enrollment or during the study.
• Treated with systemic or local diclofenac within 30 days of enrollment or during the study (except for study IMP)
• Known hypersensitivity to diclofenac, aspirin, Xarelto, coumadin, or other non-steroidal anti-inflammatory drugs (NSAIDs), including Cyclooxygenase-2 (COX-2) inhibitors.
• Any history of drug hypersensitivity, asthma, urticaria, or other significant allergic diathesis. Participants with uncomplicated seasonal allergic rhinitis can be accepted only if the expected allergy season is clearly outside enrollment / treatment periods.
• Females who are pregnant and/or lactating
• Of child-bearing potential but not willing to use adequate contraception for the duration of the study
• Participant is a current smoker and unable to abstain from smoking during the treatment periods.
• Use of any topical medication, cosmetics, cream, ointments, lotions on the treatment site 1 week prior to enrollment through EOT visit
• Use of any medication (including over-the-counter medication, dietary supplements, and herbal remedies) within 2 weeks before first scheduled study drug administration or within less than 5 times the elimination half-life of the respective drug (whichever is longer) or is anticipated to require concomitant medication during the 2-week period or at any time throughout the study. Consumption of any drug metabolizing enzyme (e.g., cytochrome P450 3A4 (CYP3A4) or other cytochrome P450 enzymes) inducing or inhibiting beverages or food (e.g., broccoli, Brussel sprouts, grapefruit, grapefruit juice, star fruit) within 3 days prior to and during each treatment period
• Participant has a known or suspected malignancy, excluding basal cell cancer unless it is associated with the treatment area.
• Participant has a positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C antibody (Anti-HCV)
• Participant has any acute or chronic condition or is using medications, which, in the investigator's opinion, would make it unsafe for the participant to participate in this study, including clinically significant abnormal laboratory values, vital signs, physical examination findings prior to randomization or during study participation.
• History or current evidence of renal disease or impaired renal function at screening as indicated by abnormal levels of serum creatinine (greater than (>) 1.43 mg/dL (milligram per deciliter)) or blood urea nitrogen (greater than or equal to (≥) 35 mg/dL) or the presence of clinical significant abnormal urinary constituents (e.g., albuminuria)
• History or current evidence of ongoing hepatic disease or impaired hepatic function at screening. A participant will be excluded if more than one of the following lab value deviations are found: 1) aspartate aminotransferase (AST) (≥ 1.5 upper limit of normal (ULN)), alanine aminotransferase (ALT) (≥ 1.5 ULN), 2) Gamma-Glutamyl Transferase (GGT) (≥ 1.5 ULN), alkaline phosphatase (ALP) (≥ 1.5 ULN), 3) total bilirubin (> 2.00 mg/dL) or creatine kinase (≥ 3 ULN). A single deviation from the above values is acceptable and will not exclude the participant, unless specifically advised by the Investigator.
• Participant has clinically relevant chronic or acute infectious illnesses or febrile infections within 2 weeks prior to the first scheduled study drug administration
• Participant has gastrointestinal bleeding issues, e.g., Gastroesophageal Reflux Disease (GERD), Peptic Ulcer Disease (PUD)
• Participant has a hospital admission or major surgery within 30 days prior to randomization.
• Participant has a donation or blood collection of more than 1 unit (approximately 450 mL(milliliter)) of blood (or blood products) or acute loss of blood during the 30 days prior to randomization.
• Participant has a history of alcohol abuse, prescription drug abuse, or illicit drug use within 6 months prior to Screening.
• Participant meets eligibility criteria, but study is filled
• Participant who is an investigational site staff member directly involved in the conduct of the study and his/her family members, site staff member otherwise supervised by the Investigator, or participant who is a Amzell B.V. employee directly involved in the conduct of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMZ001 Low dose; AMZ001 applied once daily for 7 consecutive days	Drug: Diclofenac Sodium Gel; Topical application on both knees
Experimental: AMZ001 High dose; AMZ001 applied once daily for 7 consecutive days	Drug: Diclofenac Sodium Gel; Topical application on both knees
Active Comparator: Diclofenac Sodium 1% Gel; Reference product applied four-times daily for 7 consecutive days	Drug: Diclofenac Sodium Gel; Topical application on both knees

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare exposure to diclofenac	Area under the curve from time zero to 24 hours and maximum (peak) plasma drug concentration	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameter - Cmin	Minimum plasma drug concentration (Cmin)	Day 7
Pharmacokinetic parameter - Tmax	Time to reach maximum plasma concentration (Tmax)	Day 7
Pharmacokinetic parameter - Ke	Terminal disposition rate constant (Ke)	Day 7
Pharmacokinetic parameter - Cavg	Average plasma concentration (Cavg)	Day 7
Pharmacokinetic parameter - Cmax	Maximum plasma drug concentration (Cmax)	Day 1
Pharmacokinetic parameter - Tmax	Time to reach maximum plasma concentration	Day 1
Pharmacokinetic parameter - Cavg	Average plasma concentration	Day 1
Local tolerability	Incidence of application site reactions according to the terminology of the International Contact Dermatitis Research Group	Day 1 to Day 7

Collaborators and Investigators

• Sponsor: Amzell

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2023
• Primary Completion (Actual): December 27, 2023
• Study Completion (Estimated): May 17, 2024

Study Registration Dates

• First Submitted: July 7, 2023
• First Submitted That Met QC Criteria: July 27, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Diclofenac
• Other Study ID Numbers: AMZ001-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No