Study to Assess Safety, Tolerability, and Pharmacokinetics of Oral Doses for AC430 in Healthy Subjects

Rheumatoid Arthritis Clinical Trial

Official title:

A Phase 1, Randomized, Double Blind, Placebo Controlled, Sequential, Ascending Single-Dose and Multiple-Dose First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AC430 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01287858
• Other study ID #: AC430-001
• Status: Completed
• Phase: Phase 1
• First received: January 12, 2011
• Last updated: October 29, 2015
• Start date: November 2010
• Est. completion date: June 2011

Study information

• Verified date: October 2015
• Source: Daiichi Sankyo Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

AC430 will be administered, orally under fasting conditions (fasting 4 hours before and 2 hours after dosing) with approximately 240 mL of water either once daily or twice daily. It is designed to assess the safety, tolerability, and pharmacokinetics of single and multiple oral doses of AC430.

Description:

A dose-finding study of AC430 in healthy volunteers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Important Inclusion Criteria:

1. Healthy normal males and females, age 18 to 45, inclusive, at the time of consent

2. Able to communicate effectively in the English language

3. Able to provide valid, written informed consent

4. Able to swallow up to 20 capsules of study drug

5. BMI (body mass index) ranging between 18 and 30 kg/m2, inclusive

6. Minimum weight of 50 kg

7. Serum Creatinine = ULN (upper limit of normal) and estimated creatinine clearance at screening of = 80 mL/min per the Cockcroft-Gault equation

8. Total serum bilirubin = ULN (may be repeated to confirm eligibility)

9. Serum aspartate transaminase (AST) and alanine transaminase (ALT) = ULN (may be repeated to confirm eligibility)

10. Male subjects must either be sterile or agree to use from Check-in until 90 days following the last dose of AC430, an acceptable form of birth control.

11. Female participants must be either of non-child-bearing potential or agree to use an acceptable form of birth control.

Important Exclusion Criteria:

1. History of clinically significant drug allergy

2. Participation in another clinical trial with receipt of an Investigational Product within 90 days before dose administration (or 5 half-lives, whichever is longer)

3. Major surgery within 90 days before study enrollment

4. Use of prescription, over the counter, or herbal medications or supplements, including oral contraceptives within 14 days of check-in

5. A history of drug abuse or a history of alcohol abuse within 1 year prior to Screening

6. Current or recent (within 30 days before enrollment) use of tobacco or nicotine products

7. Consumption of alcohol containing beverages > an average of 14 drinks per week or unwillingness to refrain from ethanol consumption while confined to the study unit

8. Inadequate venous access that would interfere with obtaining blood samples

9. Recipients of blood transfusion or transfusion of blood or plasma products, within 90 days before study drug administration

10. Donation of blood = 500 mL within 2 months before study drug administration

11. History or positive laboratory evidence of Human immunodeficiency virus (HIV), Hepatitis B antigen and antibody, or Hepatitis C, or history of Tuberculosis (TB) infection, or a positive result for Quantiferon Gold test

12. Prolonged average of the corrected QTc by Fridericia's correction factor (QTcF) interval on screening electrocardiogram (ECG) triplicate (= 450 ms for males and = 470 ms for females)

13. Abnormal laboratory values that are considered clinically significant by the Investigator

14. History of cancer

15. History of eating disorders within the past 3 months

16. History of a seizure disorder or clinically significant head injury

17. Positive urine drug screen for drugs of abuse including alcohol

18. Active infection within 90 days of check-in

19. Medical condition, serious intercurrent illness, cardiovascular, pulmonary, neurologic, psychiatric, renal, hepatic or gastrointestinal disease, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize subject safety or interfere with the objectives of the study

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• AC430
Healthy volunteers will either receive AC430 or placebo.

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the safety, tolerability, and pharmacokinetics of single and multiple oral doses of AC430.	Number of participants with adverse events as measurement of safety and tolerability of AC430. [Time frame: 1-28 days]; Maximum concentration (Cmax) for AC430 in plasma (measured in ng/mL) [Time frame: 1-28 days]; Tmax = Time of maximum concentration of AC430 in plasma (hr) [Time frame: 1-28 days]; AUC = Area under the curve from the time of dosing extrapolated to infinity (ng.hr/mL) [Time frame: 1-28 days]; Urine: amount of AC430 excreted in urine (Ae0-48), renal clearance (CLr) and fraction of drug excreted in urine (Fe). [Time frame: 1-28 days]	6 months	Yes
Secondary	Determine the pharmacodynamic effects of single and multiple oral doses of AC430.	Single ascending dose (SAD): Pharmacodynamics (blood analysis) of AC430 [Time Frame: up to 8 days post dose] [Designated as safety issue: No]; Multiple ascending doses (MAD): Pharmacodynamics (blood analysis) of AC430 [Time Frame: up to 17 days postdose] [Designated as safety issue: No]	Measured at specific timepoints prior to and following dosing regimen.	No