Healthy Volunteer
Conditions
Keywords
pharmacokinetics
Brief summary
The aim of the present study is to investigate the systemic bioavailability of AMZ001, applied once daily on each knee compared to Diclofenac diethylammonium gel 1.16%, applied 4 times daily on each knee, after repeated dosing in healthy subjects for 7 days The safety and local tolerability of AMZ001, applied once daily, will be evaluated after repeated dosing in healthy subjects for 7 days
Detailed description
On their both knees, participants will apply once daily AMZ001 for 7 consecutive days. Participants will also apply Diclofenac Diethylammonium 1.16% 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 two treatments in a randomized manner. Between each treatment, participant will not receive any of tested therapies during at least 21 days 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.
Interventions
topical administration
Topical administration
Sponsors
Amzell
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index (BMI) within the range of 18.0-30.0 kg/m\^2 (inclusive) at screening * Female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: * Is a WONCBP. A WOCBP must have a negative highly sensitive serum pregnancy test at screening OR * Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), preferably with low user dependency, without interruption, during trial participation and until 30 days after the last administration of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. * Participant is overtly healthy as determined by medical evaluation including medical history, full physical examination, vital signs, and ECG * Participant is free of any systemic or dermatologic disorder and chronic or acute infections, which, in the opinion of the Investigator, may interfere with the study results or increase the risk of adverse events. * Participant is a non-smoker, former smoker or stable non-smoker (= 0 cigarettes, pipes, cigars, or others) for at least 3 months prior to screening. Participant must also have abstained from use of other nicotine containing products (e.g., nicotine patch, chewing gum or e-cigarettes) for at least 3 months before screening. * Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol prior to any clinical study specific procedure.
Exclusion criteria
* Any visible skin disease, skin lesions, wounds, or a significant amount of hair at the application sites (both knees). * Any history or evidence of any clinically relevant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinologic, hematologic, immunologic, metabolic, genitourinary, pulmonary, neurologic, dermatologic, musculoskeletal, psychiatric and/or other major disease as determined by medical evaluation (including \[abbreviated\] physical examination) capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data. * Any known or suspected malignancy, excluding basal cell cancer unless it is associated with the treatment area. * Any gastrointestinal bleeding issues, e.g., Gastroesophageal Reflux Disease, Peptic Ulcer Disease. * Any hospital admission or major surgery within 30 days prior to randomization * History or current evidence of ongoing hepatic disease or impaired hepatic function at screening as indicated by diagnostic assessments * History or current evidence of renal disease or impaired renal function at screening as indicated by diagnostic assessments * Any clinically relevant history of allergic conditions requiring hospitalization or prolonged systemic treatment (including drug allergies, drug hypersensitivity, asthma, angioedema, urticaria, eczema, acute rhinitis precipitated by acetylsalicylic acid or other NSAIDs, allergies requiring therapy with corticosteroids or anaphylactic reactions), excluding allergic contact sensitizations (e.g., nickel allergy). Subjects with uncomplicated seasonal allergic rhinitis can be accepted only if the expected allergy season is clearly outside enrolment/ treatment periods. * Known or suspected hypersensitivity to diclofenac, or any components of the formulations used * Contraindications for the use of study interventions * Any clinically relevant chronic or acute infectious illnesses or febrile infections within 2 weeks prior to the first scheduled administration of study intervention * Evidence of COVID-19 signs or symptoms or confirmed COVID-19 infection within the last 2 weeks prior to screening. * Treatment with systemic or local diclofenac within 30 days of enrollment or during the study (except for study interventions). * Use of any concomitant medication or any drugs / medicines (including over-the-counter medication, dietary supplements, natural and herbal remedies) within 2 weeks before the first scheduled administration of study intervention or within less than 10 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. * Use of any topical medication, cosmetics, cream, ointments, lotions on the treatment site 2 weeks prior to enrollment through EOT visit. * Use of any investigational drug or participation in any clinical study within 30 days or 10 half-life times (if known) of study drug administered in a previous trial, whichever is longer, prior to the expected date of first administration of study intervention. * Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV) and anti-human immunodeficiency virus antibodies (anti-HIV 1 and 2 and HIV 1-p24 antigen) at screening * Positive screen for alcohol, drugs of abuse and cotinine test at screening. * Female subject who plans to become pregnant during the clinical study period and for 3 months after final study intervention administration * Donation or blood collection of more than 1 unit (approximately 450 mL) of blood (or blood products) or acute loss of blood during the 30 days prior to randomization. * Employee of the Sponsor, or Contract Research Organization (CRO) involved in the clinical study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve 0-24h | Day 7 | Area under the curve from time zero to 24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter - Cmin | Day 7 | Minimum plasma drug concentration (Cmin) |
| Pharmacokinetic Parameter - Cavg | Day 7 | Average plasma concentration (Cavg) |
| Pharmacokinetic Parameter - Tmax | Day 7 | Time to reach maximum plasma concentration (Tmax) |
| Compare Exposure to Diclofenac | Day 1 | Area under the curve from time zero to 24 hours and maximum (peak) plasma drug concentration |
| Incidence of Application Site Reactions | Day 1 to Day 7 | Number of subjects having at least one event |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AMZ001/Diclofenac Diethylamine 1.16% AMZ001 applied once daily for 7 consecutive days followed by at least 21-day washout followed by Diclofenac diethylamine 1.16% applied four times daily for 7 consecutive days | 17 |
| Diclofenac Diethylamine 1.16%/AMZ001 Reference product applied four-times daily for 7 consecutive days followed by at least 21-day washout followed by AMZ001 applied once daily for 7 consecutive days | 17 |
| Total | 34 |
Baseline characteristics
| Characteristic | AMZ001/Diclofenac Diethylamine 1.16% | Diclofenac Diethylamine 1.16%/AMZ001 | Total |
|---|---|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 12.75 | 44.5 years STANDARD_DEVIATION 9.94 | 45.8 years STANDARD_DEVIATION 11.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 17 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 15 Participants | 32 Participants |
| Sex: Female, Male Female | 11 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 34 |
| other Total, other adverse events | 5 / 33 | 8 / 34 |
| serious Total, serious adverse events | 0 / 33 | 0 / 34 |
Outcome results
Primary
Area Under the Curve 0-24h
Area under the curve from time zero to 24 hours
Time frame: Day 7
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AMZ001 | Area Under the Curve 0-24h | 281.60 h*ng/mL | Geometric Coefficient of Variation 67.1 |
| Diclofenac Diethylamine 1.16% | Area Under the Curve 0-24h | 411.35 h*ng/mL | Geometric Coefficient of Variation 57.2 |
Secondary
Compare Exposure to Diclofenac
Area under the curve from time zero to 24 hours and maximum (peak) plasma drug concentration
Time frame: Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AMZ001 | Compare Exposure to Diclofenac | 141.76 h*ng/mL | Geometric Coefficient of Variation 101.6 |
| Diclofenac Diethylamine 1.16% | Compare Exposure to Diclofenac | 86.76 h*ng/mL | Geometric Coefficient of Variation 116.3 |
Secondary
Incidence of Application Site Reactions
Number of subjects having at least one event
Time frame: Day 1 to Day 7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AMZ001 | Incidence of Application Site Reactions | 0 Participants |
| Diclofenac Diethylamine 1.16% | Incidence of Application Site Reactions | 1 Participants |
Secondary
Pharmacokinetic Parameter - Cavg
Average plasma concentration (Cavg)
Time frame: Day 7
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AMZ001 | Pharmacokinetic Parameter - Cavg | 11.733 ng/mL | Geometric Coefficient of Variation 67.1 |
| Diclofenac Diethylamine 1.16% | Pharmacokinetic Parameter - Cavg | 17.139 ng/mL | Geometric Coefficient of Variation 57.2 |
Secondary
Pharmacokinetic Parameter - Cavg
Average plasma concentration
Time frame: Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AMZ001 | Pharmacokinetic Parameter - Cavg | 5.906 ng/mL | Geometric Coefficient of Variation 101.6 |
| Diclofenac Diethylamine 1.16% | Pharmacokinetic Parameter - Cavg | 3.615 ng/mL | Geometric Coefficient of Variation 116.3 |
Secondary
Pharmacokinetic Parameter - Cmin
Minimum plasma drug concentration (Cmin)
Time frame: Day 7
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AMZ001 | Pharmacokinetic Parameter - Cmin | 5.812 ng/mL | Geometric Coefficient of Variation 73.1 |
| Diclofenac Diethylamine 1.16% | Pharmacokinetic Parameter - Cmin | 10.22 ng/mL | Geometric Coefficient of Variation 50.2 |
Secondary
Pharmacokinetic Parameter - Tmax
Time to reach maximum plasma concentration (Tmax)
Time frame: Day 7
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMZ001 | Pharmacokinetic Parameter - Tmax | 6 h |
| Diclofenac Diethylamine 1.16% | Pharmacokinetic Parameter - Tmax | 17.9830 h |
Secondary
Pharmacokinetic Parameter - Tmax
Time to reach maximum plasma concentration (Tmax)
Time frame: Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMZ001 | Pharmacokinetic Parameter - Tmax | 9.9170 h |
| Diclofenac Diethylamine 1.16% | Pharmacokinetic Parameter - Tmax | 23.8330 h |