Bioavailability
Conditions
Brief summary
The study will utilize already FDA-approved marketed diclofenac products in healthy adults to generate data for establishing rate of drug delivery comparisons between diclofenac epolamine patches and diclofenac sodium solution in healthy adults and to determine skin concentrations.
Detailed description
The study will utilize already FDA-approved marketed diclofenac products in healthy adults to generate data for establishing rate of drug delivery comparisons between diclofenac epolamine patches and diclofenac sodium solution in healthy adults and to determine skin concentrations. This study supports FDA's continuing effort to identify the most accurate, sensitive, reproducible and efficient methods to evaluate topical dermatological drug products.
Interventions
patch
solution
Sponsors
Food and Drug Administration (FDA)
University of Maryland, Baltimore
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
The same 12 volunteers received all treatments in three separate study arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Men or non-pregnant, women who are of any ethnic background between the age of 18 to 45 years old 2. Subjects must be non-smokers (must have refrained from the use of nicotine-containing substances, including tobacco products (e.g., cigarettes, cigars, chewing tobacco, snuff, gum, patches or electronic cigarettes) over the previous 2 months and are not currently using tobacco products 3. Provide written informed consent before initiation of any of the study procedures 4. Agree not to participate in another clinical trial/study during the study period or to participate in an investigational drug study for at least 1 month after the last study session 5. Able to adhere to the study protocol and study restrictions 6. Able to participate in all study sessions 7. Has a volar forearm of either at least 24 cm (9.45 inches) in length or of sufficient size that can accommodate the products to be tested in a study area that begins at least 5 cm (1.97 inches) above the wrist and ends a minimum of 0.5 cm (0.197 inches) below the antecubital fossa (i.e., the bend in the arm at the elbow). 8. Subjects have upper arms large enough to allow for placement of two 140 cm2 \[21.7 in2\] patches (distance from acromion process of the scapula to olecranon process should be a minimum of 35 cm \[13.8 inches\]; circumference of upper arms should be a minimum of 28 cm \[11.02 inches\] and 200 cm2 \[31 in2\] area for application of solution 9. Subjects deemed to be healthy as judged by the Medically Accountable Investigator (MAI) and determined by medical history, physical examination and medication history 10. Negative urine drug screening test (cannabinoids, amphetamines, barbiturates, benzodiazepine, cocaine, methadone, opiates, PCP) 11. Have normal screening laboratories for white blood cells (WBC), hemoglobin (Hgb), platelets, sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, alanine transaminase (ALT) and aspartate aminotransferase (AST) 12. Have normal screening laboratories for urine protein and urine glucose 13. Female subjects must be of non-childbearing potential (as defined as surgically sterile \[i.e. history of hysterectomy or tubal ligation\] or postmenopausal for more than 1 year), or if of childbearing potential must be non-pregnant at the time of enrollment and on the morning of each study session, and must agree to use hormonal or barrier birth control such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner 14. Agrees not to donate blood to a blood bank throughout participation in the study and for at least 3 months after last study session 15. Have a normal ECG; must not have the following to be acceptable: pathologic Q wave abnormalities, significant ST-T wave changes, left ventricular hypertrophy, right bundle branch block, left bundle branch block. (sinus rhythm is between 55-100 beats per minute) 16. Have normal vital signs: * Temperature 35-37.9°C (95-100.3°F) * Systolic blood pressure 90-165 mmHg * Diastolic blood pressure 60-100 mmHg * Heart rate 55-100 beats per minute * Respiration rate 12-20 breaths per minute
Exclusion criteria
1. Women who are pregnant, lactating, breast feeding or have a positive serum pregnancy test at enrollment or positive urine pregnancy test on the morning of the first day of each study session 2. Smokers (current use or use over the previous 2 months of nicotine-containing substances, including tobacco products (e.g., cigarettes, cigars, chewing tobacco, snuff, gum, patch or electronic cigarettes) 3. Participation in any ongoing investigational drug trial/study or clinical drug trial/study 4. History as either reported by the subject or evident to the Medically Accountable Investigator (MAI) of infectious disease or skin infection or of chronic skin disease (e.g., psoriasis, atopic dermatitis) 5. History of diabetes 6. History of significant skin cancers (e.g., melanoma, squamous cell carcinoma) except basal cell carcinomas that were superficial and did not involve the investigative sites 7. Body Mass Index (BMI) ≥30 kg/m2 8. History of chronic obstructive pulmonary disease or cor pulmonale, or substantially decreased respiratory reserve, hypoxia, hypercapnia or pre-existing respiratory depression 9. Active positive Hepatitis B, C and/or HIV serologies 10. Positive urine drug screening test 11. Use of chronic prescription medications during the period 0 to 30 days; or over-the-counter medication (e.g. antihistamines, topical corticosteroids) and short term (\<30 days) prescription medications during the period 0-3 days before a study session (vitamins, herbal supplements and birth control medications not included) 12. Currently taking daily oral nonsteroidal anti-inflammatory drug \[NSAIDs\] (aspirin, ibuprofen, naproxen, etc…) 13. Currently taking daily anticoagulants or within the past month prior to entry into the study (warfarin, heparin, rivaroxaban, dabigatran, etc…), ACE-inhibitors, cyclosporine, diuretics, lithium or methotrexate 14. Donation or loss of greater than one pint of blood within 60 days of entry to the study 15. Any prior adverse reaction or hypersensitivity to diclofenac, aspirin, ibuprofen, naproxen or other nonsteroidal anti-inflammatory drug (NSAID), other inactive ingredients in the patch or topical solution or to adhesives or tapes used to cover or tape strip the treatment sites 16. Received an experimental agent (vaccine, drug, biologic, device, blood product or medication) within 1 month before enrollment in this study or expects to receive an experimental agent during the study 17. Eat or drink anything containing alcohol within 24 hours prior to dose administration 18. Any condition that would, in the opinion of the Medically Accountable Investigator (MAI), place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol 19. Subject has an obvious difference in skin color between arms or the presence of a skin condition, excessive hair at the application site (upper arms/volar forearms), sunburn, raised moles or scars, open sores at application site (upper arms/volar forearms), scar tissue, tattoo, or coloration that would interfere with placement of diclofenac products, skin assessment, or reactions to diclofenac 20. History of asthma or urticaria,, hypertension, myocardial infarction, thrombotic events, stroke, congestive heart failure, impaired renal function or liver disease 21. History of gastrointestinal bleeding or peptic ulcer disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Diclofenac Concentrations | blood samples obtained over 51 hour time period for study session 1 and over 47 hour time period for study session 2; through study completion | Study Session 1: within 60 min prior to dosing, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 24, 27, 30, 32, 51 h Study Session 2: within 60 min prior to dosing, 1, 2, 3, 4, 5, 6, 7, 23, 26, 29, 31, 47 h Study Session 3: no blood samples obtained |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diclofenac Study Session 1. diclofenac epolamine patch Study Session 2. diclofenac sodium solution Study Session 3. diclofenac epolamine patch pieces and diclofenac sodium solution | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Diclofenac |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 36 years STANDARD_DEVIATION 6.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 12 / 12 | 12 / 12 | 12 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Serum Diclofenac Concentrations
Study Session 1: within 60 min prior to dosing, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 24, 27, 30, 32, 51 h Study Session 2: within 60 min prior to dosing, 1, 2, 3, 4, 5, 6, 7, 23, 26, 29, 31, 47 h Study Session 3: no blood samples obtained
Time frame: blood samples obtained over 51 hour time period for study session 1 and over 47 hour time period for study session 2; through study completion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac Epolamine Patches | Serum Diclofenac Concentrations | 5.6 ng/mL | Standard Deviation 10.8 |
| Diclofenac Sodium Solution | Serum Diclofenac Concentrations | 40.0 ng/mL | Standard Deviation 54.3 |