A Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects

Healthy Subjects Clinical Trial

Official title:

A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Multi-Part, Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03767855
• Other study ID #: CY 6011
• Status: Completed
• Phase: Phase 1
• Start date: December 4, 2018
• Est. completion date: January 3, 2020

Study information

• Verified date: January 2020
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purposes of this study are to:

1. Learn about the safety of CK-3773274 after a single dose and multiple doses in healthy subjects.

2. Learn how healthy subjects tolerate CK-3773274 after a single dose and multiple doses.

3. Find out how much CK-3773274 is in the blood after a single dose and multiple doses.

4. Determine the effect of doses of CK-3773274 on the pumping function of the heart.

5. Evaluate the effect of cytochrome genetic variants on how the body metabolizes CK-3773274.

6. Evaluate the effect of a meal on how much CK-3773274 is in the blood in healthy adult subjects.

7. Evaluate whether the amount of CK-3773274 in the blood is the similar for both the tablet and granules in capsule forms of the drug.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: January 3, 2020
• Est. primary completion date: January 3, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Males and females (of non-childbearing potential) between 18 and 55 years of age, inclusive

2. Body weight > 55.0 kg and body mass index within 18.0 to 32.0 kg/m2, inclusive

3. Normal cardiac structure and function, or if abnormalities are present, they are deemed not clinically significant

4. Normal to high left ventricular ejection fraction.

5. Normal electrocardiogram (ECG) or, if abnormalities are present, they are deemed not clinically significant

6. Clinical laboratory findings within normal range

7. Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C antibody), and negative human immunodeficiency virus antibody screens

8. Willing and able to refrain from strenuous exercise (eg, activity which could be expected to cause muscle soreness)

9. For Arms 5 and 6 only: Subject is a CYP2D6 poor metabolizer

Exclusion Criteria:

1. History of any significant illness or disorder

2. History of stomach or intestinal surgery or resection (appendectomy, hernia repair, and/or cholecystectomy will be allowed)

3. A clinically significant illness within 4 weeks of Check-in

4. Inability to swallow capsules or tablets

5. History of or current substance abuse (drug or alcohol), known drug or alcohol dependence within the last 2 years prior to Screening, or positive test for drugs of abuse during the screening period

6. Use of any tobacco-containing or nicotine-containing products within 3 months prior to Check-in

7. Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days prior to Check-in

8. Any blood donation within 60 days of dosing, plasma donation within 30 days of dosing, or receipt of blood products within 2 months prior to Check-in

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Healthy Subjects
• Hypertrophy
• Symptomatic Obstructive Hypertrophic Cardiomyopathy

Intervention

Drug:
• CK-3773274 - Granules in Capsule
CK-3773274 formulated as granules in capsule
• Placebo - Granules in Capsule
Placebo formulated as granules in capsule
• CK-3773274 - Tablets
CK-3773274 formulated as tablets

Locations

Country	Name	City	State
United States	Clinical Site	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Cytokinetics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse events and Safety Signals observed during single and multiple ascending doses of CK-3773274 administered orally to healthy adult subjects.	Subject incidence of AEs, SAEs, and reduced LVEF	SAD Cohorts: Day -1 - Day 10; CYP2D6 Cohort: Day -1 - Day - 24; MAD Cohorts: Day -1 - Day 27; Food Effect Cohort: Day -1 - Day 24; relative Bioavailability Cohort: Day -1 - Day 29
Secondary	Cmax of CK-3773274 after single and multiple ascending doses	Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects	SAD Cohorts: Day 1; CYP2D6 Cohort: Day 1; MAD Cohorts: Day 14 or Day 17; Food Effect Cohort: Day 15; Relative Bioavailability Cohort: Day 15
Secondary	Change in absolute reduction in ejection fraction relative to baseline with doses of CK-3773274	Changes from baseline in LVEF as measured by echocardiography with doses of CK-3773274	Time Frame for SAD Cohorts: Day -1 - Day 10; Time Frame for CYP2D6 Cohort: Day -1 - Day 24; Time Frame for MAD Cohorts: Day -1 - Day 27
Secondary	Assess the effect of CYP2D6 genetic variants on the PK of CK-3773274	Maximum concentration after dosing (Cmax) following a single dose administered to CYP2D6 poor metabolizers	Day -1 - Day 24
Secondary	Assess the effect of a meal on how much CK-3773274 is in the blood in healthy subjects	Maximum concentration after dosing (Cmax) following single and multiple doses of CK-3773274 administered to healthy subjects in fed and fasted states	Day -1 - Day 24
Secondary	Relative bioavailability of CK-3773274 formulated as granules in capsule versus a tablet in healthy adult subjects	PK parameters such as AUC calculated using plasma concentrations of CK-3773274	Time Frame for Bioavailability Cohort: Day -1 - Day 29