Symptomatic Obstructive Hypertrophic CardiomyopathyPhase 1NCT03767855
A Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects
A Phase 1 study testing CK-3773274 - Granules in Capsule and CK-3773274 - Tablets in people with Symptomatic Obstructive Hypertrophic Cardiomyopathy and Healthy Subjects, run by Cytokinetics at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Symptomatic Obstructive Hypertrophic Cardiomyopathy, Healthy Subjects
- What is being tested?
- CK-3773274 - Granules in Capsule and CK-3773274 - Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 114 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Dec 2018to 3 Jan 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males and females (of non-childbearing potential) between 18 and 55 years of age, inclusive
- Body weight > 55.0 kg and body mass index within 18.0 to 32.0 kg/m2, inclusive
- Normal cardiac structure and function, or if abnormalities are present, they are deemed not clinically significant
- Normal to high left ventricular ejection fraction.
- Normal electrocardiogram (ECG) or, if abnormalities are present, they are deemed not clinically significant
- Clinical laboratory findings within normal range
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- Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C antibody), and negative human immunodeficiency virus antibody screens
- Willing and able to refrain from strenuous exercise (eg, activity which could be expected to cause muscle soreness)
- For Arms 5 and 6 only: Subject is a CYP2D6 poor metabolizer
Who cannot join
- History of any significant illness or disorder
- History of stomach or intestinal surgery or resection (appendectomy, hernia repair, and/or cholecystectomy will be allowed)
- A clinically significant illness within 4 weeks of Check-in
- Inability to swallow capsules or tablets
- 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
- Use of any tobacco-containing or nicotine-containing products within 3 months prior to Check-in
- Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days prior to Check-in
- 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 locations and contacts
1 site in 1 country.
About this study
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
The purposes of this study are to:
- Learn about the safety of CK-3773274 after a single dose and multiple doses in healthy subjects.
- Learn how healthy subjects tolerate CK-3773274 after a single dose and multiple doses.
- Find out how much CK-3773274 is in the blood after a single dose and multiple doses.
- Determine the effect of doses of CK-3773274 on the pumping function of the heart.
- Evaluate the effect of cytochrome genetic variants on how the body metabolizes CK-3773274.
- Evaluate the effect of a meal on how much CK-3773274 is in the blood in healthy adult subjects.
- 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.
- Being tested
- CK-3773274 - Granules in Capsule, Placebo - Granules in Capsule, CK-3773274 - Tablets
- Keywords
- CK-3773274, CK-274, obstructive hypertrophic cardiomyopathy, oHCM, aficamten
- Medical subject headings
- Cardiomyopathy, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CK-3773274 - Granules in CapsuleDrug
CK-3773274 formulated as granules in capsule
Placebo - Granules in CapsuleDrug
Placebo formulated as granules in capsule
CK-3773274 - TabletsDrug
CK-3773274 formulated as tablets
| Study group | Role | What they receive |
|---|---|---|
| CK-3773274 for SAD Cohorts | Experimental | Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274 Receives: Drug: CK-3773274 - Granules in Capsule |
| Placebo for SAD Cohorts | Placebo comparator | Subjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo Receives: Drug: Placebo - Granules in Capsule |
| CK-3773274 for MAD Cohorts | Experimental | Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274 Receives: Drug: CK-3773274 - Granules in Capsule |
| Placebo for MAD Cohorts | Placebo comparator | Subjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo Receives: Drug: Placebo - Granules in Capsule |
| CK-3773274 for CYP2D6 Cohort | Experimental | Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274 Receives: Drug: CK-3773274 - Granules in Capsule |
| Placebo for CYP2D6 Cohort | Placebo comparator | Subjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo Receives: Drug: Placebo - Granules in Capsule |
| Food Effect | Experimental | Subjects will be administered CK-3773274 with and without food in a randomized cross-over fashion Receives: Drug: CK-3773274 - Granules in Capsule |
| Relative Bioavailability | Experimental | Subjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion. Receives: Drug: CK-3773274 - Granules in Capsule; Drug: CK-3773274 - Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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 outcomes (5)
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
Measured: 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
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
Measured: 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
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
Measured: Day -1 - Day 24
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
Measured: Day -1 - Day 24
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
Measured: Time Frame for Bioavailability Cohort: Day -1 - Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2018
- Study start4 Dec 2018
- Primary completion3 Jan 2020
- Study completion3 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Symptomatic Obstructive Hypertrophic CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytokinetics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director MD, Study director, Cytokinetics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03767855
- Sponsor's protocol ID
- CY 6011
- Status last verified
- Jan 2020
- First submitted
- 3 Dec 2018
- Last updated
- 24 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Malik FI, Robertson LA, Armas DR, Robbie EP, Osmukhina A, Xu D, Li H, Solomon SD. A Phase 1 Dose-Escalation Study of the Cardiac Myosin Inhibitor Aficamten in Healthy Participants. JACC Basic Transl Sci. 2022 Aug 10;7(8):763-775. doi: 10.1016/j.jacbts.2022.04.008. eCollection 2022 Aug.
PubMed 36061336
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03767855
- Acronym / sponsor ID
- CY 6011
- Keywords
- CK-3773274, CK-274, obstructive hypertrophic cardiomyopathy, oHCM, aficamten
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- CytokineticsIndustry (pharma, biotech, devices)
- Study start
- 4 Dec 2018 (actual)
- Primary completion
- 3 Jan 2020 (actual)
- Study completion
- 3 Jan 2020 (actual)
- First posted
- 7 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purposes of this study are to:
- Learn about the safety of CK-3773274 after a single dose and multiple doses in healthy subjects.
- Learn how healthy subjects tolerate CK-3773274 after a single dose and multiple doses.
- Find out how much CK-3773274 is in the blood after a single dose and multiple doses.
- Determine the effect of doses of CK-3773274 on the pumping function of the heart.
- Evaluate the effect of cytochrome genetic variants on how the body metabolizes CK-3773274.
- Evaluate the effect of a meal on how much CK-3773274 is in the blood in healthy adult subjects.
- 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| CK-3773274 for SAD Cohorts | Experimental | Drug: CK-3773274 - Granules in CapsuleSubjects will be assigned to one of 8 planned dose cohorts and receive single doses of CK-3773274 |
| Placebo for SAD Cohorts | Placebo comparator | Drug: Placebo - Granules in CapsuleSubjects will be assigned to one of 8 planned dose cohorts and receive single doses of placebo |
| CK-3773274 for MAD Cohorts | Experimental | Drug: CK-3773274 - Granules in CapsuleSubjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of CK-3773274 |
| Placebo for MAD Cohorts | Placebo comparator | Drug: Placebo - Granules in CapsuleSubjects will be assigned to one of 3 planned dose cohorts and receive multiple doses of placebo |
| CK-3773274 for CYP2D6 Cohort | Experimental | Drug: CK-3773274 - Granules in CapsuleSubjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of CK-3773274 |
| Placebo for CYP2D6 Cohort | Placebo comparator | Drug: Placebo - Granules in CapsuleSubjects with CYP2D6 poor metabolizer phenotype will be assigned to receive a single dose of placebo |
| Food Effect | Experimental | Drug: CK-3773274 - Granules in CapsuleSubjects will be administered CK-3773274 with and without food in a randomized cross-over fashion |
| Relative Bioavailability | Experimental | Drug: CK-3773274 - Granules in Capsule, Drug: CK-3773274 - TabletsSubjects will be administered CK-3773274 as granules in a capsule and as a tablet in a randomized cross-over fashion. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Males and females (of non-childbearing potential) between 18 and 55 years of age, inclusive
- Body weight > 55.0 kg and body mass index within 18.0 to 32.0 kg/m2, inclusive
- Normal cardiac structure and function, or if abnormalities are present, they are deemed not clinically significant
- Normal to high left ventricular ejection fraction.
- Normal electrocardiogram (ECG) or, if abnormalities are present, they are deemed not clinically significant
Key exclusion criteria (8 listed)
- History of any significant illness or disorder
- History of stomach or intestinal surgery or resection (appendectomy, hernia repair, and/or cholecystectomy will be allowed)
- A clinically significant illness within 4 weeks of Check-in
- Inability to swallow capsules or tablets
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CK-3773274 - Granules in CapsuleCK-3773274 formulated as granules in capsule | Drug | CK-3773274 for CYP2D6 Cohort, CK-3773274 for MAD Cohorts, CK-3773274 for SAD Cohorts, Food Effect, Relative Bioavailability |
| Placebo - Granules in CapsulePlacebo formulated as granules in capsule | Drug | Placebo for CYP2D6 Cohort, Placebo for MAD Cohorts, Placebo for SAD Cohorts |
| CK-3773274 - TabletsCK-3773274 formulated as tablets | Drug | Relative Bioavailability |
Primary outcome
Incidence of Adverse events and Safety Signals observed during single and multiple ascending doses of CK-3773274 administered orally to healthy adult subjects.
Time frame: 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
Subject incidence of AEs, SAEs, and reduced LVEF
5 secondary outcomes
Cmax of CK-3773274 after single and multiple ascending doses
Time frame: 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
Change in absolute reduction in ejection fraction relative to baseline with doses of CK-3773274
Time frame: 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
Assess the effect of CYP2D6 genetic variants on the PK of CK-3773274
Time frame: Day -1 - Day 24
Assess the effect of a meal on how much CK-3773274 is in the blood in healthy subjects
Time frame: Day -1 - Day 24
Relative bioavailability of CK-3773274 formulated as granules in capsule versus a tablet in healthy adult subjects
Time frame: Time Frame for Bioavailability Cohort: Day -1 - Day 29
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2025.
- Derived from this study: PubMed 36061336Malik FI, Robertson LA, Armas DR, Robbie EP, Osmukhina A, Xu D, Li H, Solomon SD. A Phase 1 Dose-Escalation Study of the Cardiac Myosin Inhibitor Aficamten in Healthy Participants. JACC Basic Transl Sci. 2022 Aug 10;7(8):763-775. doi: 10.1016/j.jacbts.2022.04.008. eCollection 2022 Aug.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director MD study director
Cytokinetics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CK-3773274 - Granules in Capsule and CK-3773274 - Tablets in people with Symptomatic Obstructive Hypertrophic Cardiomyopathy and Healthy Subjects, run by Cytokinetics at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse events and Safety Signals observed during single and multiple ascending doses of CK-3773274 administered orally to healthy adult subjects. (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03767855, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2025.