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

Cytokinetics

Status and phase: Completed; Phase 1

Conditions: Symptomatic Obstructive Hypertrophic Cardiomyopathy; Healthy Subjects

Treatments: Drug: CK-3773274 - Tablets; Drug: Placebo - Granules in Capsule; Drug: CK-3773274 - Granules in Capsule

Study type: Interventional

Funder types: Industry

Identifiers

NCT03767855

CY 6011

Details and patient eligibility

About

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.

Enrollment: 114 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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114 participants in 8 patient groups, including a placebo group

CK-3773274 for SAD Cohorts

Experimental group

Description:

Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274

Treatment:

Drug: CK-3773274 - Granules in Capsule

Placebo for SAD Cohorts

Placebo Comparator group

Description:

Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo

Treatment:

Drug: Placebo - Granules in Capsule

CK-3773274 for MAD Cohorts

Experimental group

Description:

Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274

Treatment:

Drug: CK-3773274 - Granules in Capsule

Placebo for MAD Cohorts

Placebo Comparator group

Description:

Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo

Treatment:

Drug: Placebo - Granules in Capsule

CK-3773274 for CYP2D6 Cohort

Experimental group

Description:

Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274

Treatment:

Drug: CK-3773274 - Granules in Capsule

Placebo for CYP2D6 Cohort

Placebo Comparator group

Description:

Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo

Treatment:

Drug: Placebo - Granules in Capsule

Food Effect

Experimental group

Description:

Subjects will be administered CK-3773274 with and without food in a randomized cross-over fashion

Treatment:

Drug: CK-3773274 - Granules in Capsule

Relative Bioavailability

Experimental group

Description:

Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion.

Treatment:

Drug: CK-3773274 - Granules in Capsule

Drug: CK-3773274 - Tablets