RTA 408 Lotion in Healthy Volunteers
Status: | Completed |
---|---|
Conditions: | Healthy Studies |
Therapuetic Areas: | Other |
Healthy: | No |
Age Range: | 18 - 65 |
Updated: | 5/5/2014 |
Start Date: | December 2013 |
End Date: | April 2014 |
A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of RTA 408 Lotion in Healthy Volunteers
This study is a first-in-human study of a topical dermal lotion formulation of RTA 408, a
novel small molecule which suppresses oxidative stress and inflammation. In this study, the
safety, local pharmacodynamics (PD), and systemic pharmacokinetics (PK) of RTA 408 will be
evaluated following topical application of RTA 408 Lotion to healthy volunteers. This study
will be conducted in three parts. In Part A of the study, healthy volunteers will have RTA
408 Lotion Vehicle and RTA 408 Lotion (0.5%, 1%, and 3%) applied to a small skin surface
area (four individual 4-cm2 sites; 16 cm2 total area) twice daily for 14 days to assess the
local skin tolerability, local PD, and systemic PK of these treatments. Part B will be
conducted after completion of Part A and will assess the safety, tolerability, local PD, and
systemic PK of RTA 408 Lotion applied topically twice daily for 14 days to a larger skin
surface area (~100 cm2). Part C will be conducted after completion of Part B and will assess
the safety, tolerability, local PD, and systemic PK of RTA 408 Lotion applied topically
twice daily for 28 days to a larger skin surface area (~500 cm2). The maximum tolerated
drug concentration in Part A will be used in Part B and Part C.
Approximately 32 healthy adult volunteers will be enrolled in this study with 12 volunteers
in Part A and 10 volunteers each, in Parts B and C.
novel small molecule which suppresses oxidative stress and inflammation. In this study, the
safety, local pharmacodynamics (PD), and systemic pharmacokinetics (PK) of RTA 408 will be
evaluated following topical application of RTA 408 Lotion to healthy volunteers. This study
will be conducted in three parts. In Part A of the study, healthy volunteers will have RTA
408 Lotion Vehicle and RTA 408 Lotion (0.5%, 1%, and 3%) applied to a small skin surface
area (four individual 4-cm2 sites; 16 cm2 total area) twice daily for 14 days to assess the
local skin tolerability, local PD, and systemic PK of these treatments. Part B will be
conducted after completion of Part A and will assess the safety, tolerability, local PD, and
systemic PK of RTA 408 Lotion applied topically twice daily for 14 days to a larger skin
surface area (~100 cm2). Part C will be conducted after completion of Part B and will assess
the safety, tolerability, local PD, and systemic PK of RTA 408 Lotion applied topically
twice daily for 28 days to a larger skin surface area (~500 cm2). The maximum tolerated
drug concentration in Part A will be used in Part B and Part C.
Approximately 32 healthy adult volunteers will be enrolled in this study with 12 volunteers
in Part A and 10 volunteers each, in Parts B and C.
Inclusion Criteria:
1. Subjects must voluntarily give written informed consent and agree to comply with
visit schedule including willingness to remain at the study site;
2. Subjects must be adults (male or female), ages 18 to 65, inclusive;
3. Subjects must have healthy skin on which reddening can easily be recognized
(Fitzpatrick type I-IV skin);
4. The planned application site must have unbroken skin (ie, free from cuts, scratches,
and abrasions), and be free of excessive hair, tattoos, or other abnormality that, in
the Investigator's judgement, would interfere with the conduct of the study;
5. Subjects must have a body mass index (BMI) of ≥18 kg/m2 and ≤32 kg/m2;
6. Women must be of non-childbearing potential and may not be pregnant, lactating, or
breast-feeding.
7. Male subjects must agree that they and any female partners will use 2 acceptable
forms of contraception, 1 of which must be a condom, until 3 months after the last
dose of study drug.
Exclusion Criteria:
1. Persons with Fitzpatrick skin types V or VI;
2. Presence of active inflammatory dermatoses (eg, atopic dermatitis, psoriasis),
bacterial, viral, or fungal skin infections;
3. History of clinically significant drug allergies including allergies to any of the
components of the investigational product and/or clinically significant food
allergies as determined by the Investigator;
4. Use of any alcohol or methylxanthine-containing beverages or food (eg, coffee, tea,
cola, chocolate, and "power drinks") from 72 hours prior to the first dose of study
drug until after the last protocol specified blood sample;
5. Use of any tobacco products, nicotine-containing products, or pharmacologic smoking
cessation therapy during the 3 months immediately prior to the first dose of study
drug, and/or not willing or able to refrain from use of any of these products for the
duration of the study until after the last protocol specified blood sample;
6. History of alcohol abuse within 2 years of the Screening Visit, in the judgment of
the Investigator, or average weekly alcohol consumption of >14 alcoholic drinks. One
drink is defined as 1 glass of beer (approximately 10 oz to 12 oz) or 1 can (12 oz)
of beer, 1 glass of wine (approximately 4 oz to 5 oz), or 1 glass of distilled
spirits (hard liquor) containing 1 oz of the liquor (1 oz of liquid is approximately
30 mL);
7. Positive breath test for alcohol at the Screening Visit or at Day -1;
8. History of drug abuse within 2 years of the Screening Visit, in the judgment of the
Investigator;
9. Positive urine test for cotinine or drugs of abuse (ie, opiates, methadone, cocaine,
amphetamines, cannabinoids, barbiturates, benzodiazepines) at the Screening Visit or
at Day -1;
10. Not willing to abstain from strenuous exercise (eg, heavy lifting, weight training,
calisthenics, aerobics) for at least 48 hours prior to admission to the
investigational site until after the last protocol specified blood sample;
11. Use of substances known to be strong inhibitors or inducers of Cytochrome P450
(CYP450) enzymes (eg, ritonavir, ketoconazole, nefazodone, grapefruit juice) within
14 days prior to the first dose of study drug through the last study visit. Chronic
exposure to enzyme inducers such as paint solvents or pesticides or other
investigational drug use within 30 days prior to study drug administration;
12. Use of prescription drugs, dietary supplements, or herbal remedies (including
products applied topically) within 14 days or 5 half-lives (whichever is longer)
prior to the first dose of study drug; use of non-prescription drugs or vitamins
(including products applied topically) within 7 days prior to the first dose of study
drug; or unwillingness to refrain from taking any such medication until after the
last protocol specified blood sample;
13. Donation of whole blood >450 mL or blood products within 56 days prior to admission
to the investigational site;
14. Use of any investigational drug within 30 days or 5 half-lives of the previous
investigational drug prior to the first dose of study drug in this study, whichever
is longer;
15. Positive screen for human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis
C at the Screening Visit;
16. Acute illness accompanied by temperature ≥101○F within 5 days prior to study drug
administration;
17. Presence or history of cancer within 5 years prior to the Screening Visit (other than
basal cell skin cancer in a location other than the back and without active lesions
and adequately treated carcinoma in situ of cervix);
18. Presence or history of any significant cardiovascular, gastrointestinal, hepatic,
renal, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic
disease
19. Presence of any other condition (including surgery) known to interfere with the
absorption, distribution, metabolism, or excretion of medicines. History of
appendectomy and cholecystectomy is permitted;
20. Any abnormal clinical laboratory value or abnormal electrocardiogram (ECG) finding at
the Screening Visit or at Day -1 that is considered clinically significant by the
Investigator;
21. International Normalized Ratio (INR) >1.5 at the Screening Visit;
22. Men whose female partner is pregnant or lactating, or who plans to become pregnant
during the study or within 3 months after the end of the study;
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