Safety, Tolerability and PK Study of AK0529 in Healthy Human

Respiratory Syncytial Virus Infections Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of AK0529 When Administered Orally in Healthy Male and Female Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02297594
• Other study ID #: AK0529-1001
• Status: Completed
• Phase: Phase 1
• First received: November 11, 2014
• Last updated: October 19, 2015
• Start date: October 2014
• Est. completion date: June 2015

Study information

• Verified date: October 2015
• Source: Ark Biosciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety, tolerability and PK of single and multiple ascending dose of AK0529 when administered orally in healthy subjects

Description:

This is a Phase 1, first-in-man, single-center, randomized, double blind, placebo controlled single and multiple ascending dose study in healthy male and female volunteers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Must be healthy males, or healthy females of non-childbearing potential or surgically sterilized or post-menopausal (amenorrhea for at least 1 year and confirmed by a follicle stimulating hormone [FSH] result of > 20 IU/mL).

2. Must be aged 18 to 55 years of age inclusive.

3. Must have body mass index (BMI) of 18.0 to 31.0 kg/m2 inclusive.

4. Must have total body weight =50 kg at screening but =100 Kg.

5. Must be willing and able to communicate and participate in the whole study.

6. Must provide written informed consent.

7. Must agree to use an adequate method of contraception (as defined in Section 4.2.1).

8. Must have AST, ALT, total bilirubin, urea, creatinine and hemoglobin within the laboratory reference range at screening and Day -1.

9. Must have QTcF <450 ms, QTcB <450 ms and PR interval <210 ms for screening, Day -1 and pre-dose ECG measurements, and not have any degree of heart block or conduction abnormality.

10. Must have serology demonstrating they are free from infection with hepatitis B, hepatitis C, and human immunodeficiency virus (HIV-1 and HIV-2)

Exclusion Criteria:

1. Male subjects who have currently pregnant partners or who have partners planning to become pregnant during the duration of the study.

2. Evidence or history of clinical significant oncological, pulmonary, chronic respiratory, hepatic, cardiovascular, hematological, metabolic, neurological, immunological, nephrological, endocrine or psychiatric disease, or current infection.

3. Clinically relevant (as decided by the investigator and the medical monitor) abnormalities in the ECG (12 standard leads) including any degree of heart block, including asymptomatic bundle branch block.

4. Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval.

5. History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia.

6. Electrolyte disturbances, particularly hypokalemia hypocalcemia or hypomagnesemia.

7. Any condition that could possibly affect drug absorption, e.g. gastrectomy or diarrhea.

8. History of post-antibiotic colitis.

9. History of any drug or alcohol abuse in the past 2 years prior to screening.

10. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = 400 mL beer, 25 mL of 40% spirit or a 75 mL glass of wine).

11. Subjects who have a urine cotinine greater than 500 ng/mL at screening will be excluded. Subjects who are tobacco users (including smokers and users of snuff, chewing tobacco and other nicotine or nicotine-containing products) must have stopped use at least 90 days before screening.

12. Receipt of an investigational drug or participation in another clinical research study within 90 days prior to drug administration.

13. Subjects who are study site employees, or immediate family members of a study site or sponsor employee.

14. Subjects who have previously been enrolled and dosed in this study, except subjects undergoing repeat dosing in Cohort 4F (the fed PK cohort of the SAD part of the study).

Other protocol defined inclusion/exclusion criteria may apply.

Study Design

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

Related Conditions & MeSH terms

• Respiratory Syncytial Virus Infections
• Virus Diseases

Intervention

Drug:
• AK0529
AK0529 capsule for oral administration
• Placebo
Sugar placebo capsule for oral administration

Locations

Country	Name	City	State
Australia	Q-Pharm Pty Ltd QIMR Berghofer & Royal Brisbane and Women's Hospital Campus	Brisbane	Queensland

Sponsors (1)

Lead Sponsor	Collaborator
Ark Biosciences Inc.

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events, serious adverse events		Screening to Day 14 - 21	Yes
Secondary	Pharmacokinetics of single dose study: Area Under Curve (AUC)		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 and 48 hours post-dose	No
Secondary	Pharmacokinetics of single dose study: Observed Maximum plasma concentration (Cmax)		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 and 48 hours post-dose	No
Secondary	Pharmacokinetics of single dose study: half-life (t1/2)		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 and 48 hours post-dose	No
Secondary	Pharmacokinetics of single dose study: time to maximum plasma concentration (tmax)		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 and 48 hours post-dose	No
Secondary	Pharmacokinetics of single dose study: Volume of distribution		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 and 48 hours post-dose	No
Secondary	Pharmacokinetics of single dose study: Clearance		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 and 48 hours post-dose	No
Secondary	Pharmacokinetics of multiple dose study:Area Under Curve (AUC)		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day1 and pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 hours post-dose on Day 7 and at 24 hours (Day 8) and at 48 hours (Day 9)	No
Secondary	Pharmacokinetics of multiple dose study: Observed Maximum plasma concentration (Cmax)		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day1 and pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 hours post-dose on Day 7 and at 24 hours (Day 8) and at 48 hours (Day 9)	No
Secondary	Pharmacokinetics of multiple dose study: half-life (t1/2)		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day1 and pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 hours post-dose on Day 7 and at 24 hours (Day 8) and at 48 hours (Day 9)	No
Secondary	Pharmacokinetics of multiple dose study: time to maximum plasma concentration (tmax)		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day1 and pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 hours post-dose on Day 7 and at 24 hours (Day 8) and at 48 hours (Day 9)	No
Secondary	Pharmacokinetics of multiple dose study:Volume of distribution		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day1 and pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 hours post-dose on Day 7 and at 24 hours (Day 8) and at 48 hours (Day 9)	No
Secondary	Pharmacokinetics of multiple dose study: clearance		pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day1 and pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 hours post-dose on Day 7 and at 24 hours (Day 8) and at 48 hours (Day 9)	No