Study to Evaluate the Effect of Aficamten Administration on QT/QTc Interval

Overseen By Study Director Cytokinetics, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Cytokinetics

Disqualifiers: Alcohol, Drug abuse, others

Compensation: Varies

Number of Visits: Unknown

44 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the study is for healthy participants, it's likely that you should not be on any regular medications.

What safety data exists for Aficamten Administration or similar treatments?

In a study involving 430 healthy volunteers, the overall incidence of adverse events was 13.5%, with more events occurring in those taking active drugs compared to placebo. Common side effects included headaches, and there were no deaths or life-threatening events reported. ^{1 2 3 4 5}

How does the drug flibanserin differ from other treatments for hypoactive sexual desire disorder?

Flibanserin is unique because it is specifically designed to be taken at bedtime, which is different from other treatments that may not have specific timing requirements. It also carries a warning about the risk of severe low blood pressure and fainting when used with alcohol, which is a consideration not typically associated with other treatments for this condition. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial tests aficamten, a drug, to see how it affects the heart's electrical activity. Healthy participants are used to get clear results without other health issues interfering. The study checks if aficamten changes the heart's rhythm.

Research Team

Cytokinetics, MD

Principal Investigator

Cytokinetics

Eligibility Criteria

Inclusion Criteria

Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 at the screening visit.

Continuous non-smoker who has not used nicotine- and tobacco-containing products for at least 3 months prior to the first dosing based on participant self-reporting.

Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, and vital signs, as deemed by the PI or designee, including the following:

Exclusion Criteria

You have a history of using drugs or alcohol excessively in the past two years.

History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A: Dose Finding

Open-label, single ascending dose study to identify the dose for Part B

8 weeks

Part B: TQT Study

Randomized, double-blind, placebo- and positive-controlled, single-dose, 3-way crossover study to evaluate the effect of aficamten on QT/QTc interval

14.5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Aficamten Administration

Participant Groups

Group I: Part B (TQT Study): Aficamten Experimental Treatment 1 Intervention

Participants will receive a single oral dose of aficamten. The dose will be determined based on review of Part A PK parameters, echocardiogram parameters, safety, and tolerability for aficamten.

Group II: Part A (Dose Finding Cohort 3): Aficamten 100 mg Experimental Treatment 1 Intervention

Participants in this arm will receive a single oral dose up to 100 mg aficamten.

Group III: Part A (Dose Finding Cohort 2): Aficamten 75 mg Experimental Treatment 1 Intervention

Participants in this arm will receive a single oral dose up to 75 mg aficamten.

Group IV: Part A (Dose Finding Cohort 1): Aficamten 50 mg Experimental Treatment 1 Intervention

Participants in this arm will receive a single oral dose of 50 mg aficamten.

Group V: Part B (TQT Study): Moxifloxacin 400 mg Active Control 1 Intervention

Participants will receive a single oral dose of 400 mg moxifloxacin

Group VI: Part B (TQT Study): Aficamten-matching Placebo Placebo Group 1 Intervention

Participants in this arm will receive a single oral dose of aficamten-matching placebo.

Who Is Running the Clinical Trial?

Cytokinetics

Lead Sponsor

Trials

44

Recruited

17,500+

Findings from Research

In a review of 231 randomized placebo-controlled clinical trials, it was found that a staggering 96.8% of adverse events (AEs) reported in patients taking active drugs were nonspecific, meaning they were not directly related to the medication.

The study revealed strong correlations between AE rates in placebo and active-drug groups, indicating that many reported AEs may not be caused by the drug itself, which raises concerns about the reliability of clinical trial data in assessing drug tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials. Mahr, A., Golmard, C., Pham, E., et al.[2022]

The study analyzed 345,662 spontaneous reports of adverse drug reactions (ADRs) submitted to the German Federal Institute for Drugs and Medical Devices, revealing a steady increase in reports since 1978, primarily due to stricter legal reporting requirements.

The most commonly reported ADRs were linked to drugs for nervous system disorders, with significant differences in reporting patterns between physicians and patients, suggesting a need for better patient education on potential ADRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent Adverse Drug Reactions, and Medication Groups under Suspicion. Dubrall, D., Schmid, M., Alešik, E., et al.[2023]

In a review of 24 Phase I studies involving 430 healthy male volunteers over 5 years, the overall incidence of adverse events was 13.5%, with a higher rate for active drug treatments (15.3%) compared to placebo (7.4%).

Severe adverse events occurred in 20 cases (0.36%), but there were no deaths or life-threatening incidents, indicating that while adverse events are common, they are generally not severe in Phase I trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase one studies: a study in 430 healthy volunteers. Sibille, M., Deigat, N., Olagnier, V., et al.[2019]

A review of 73 migraine drug trials published between 2010 and 2015 found that while a majority reported adverse events, only 41% included this information in their abstracts, highlighting a gap in transparency.

The study emphasizes the need for all randomized controlled trials on migraine treatments to consistently report adverse events in their abstracts to better assess the safety and tolerability of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the reporting of adverse events in controlled clinical trials conducted in 2010-2015 on migraine drug treatments. Tfelt-Hansen, P., Lindqvist, JK., Do, TP.[2019]

The recent fatal adverse event in the BIA-102474-101 clinical trial highlights significant limitations in the current safety review process for first-into-human trials, despite previous trials with similar compounds being conducted without incident.

To improve safety in future trials, it is crucial to implement sequential dosing strategies, thorough reviews of preclinical toxicity studies, and systematic risk assessments, especially for novel compounds that may pose higher risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of the BIA-102474-101 study for review of first-into-human clinical trials. Eddleston, M., Cohen, AF., Webb, DJ.[2021]

In a study involving 24 healthy premenopausal women, flibanserin taken at bedtime after moderate alcohol consumption was well-tolerated, showing no significant increase in hypotension or syncope compared to placebo.

The study found that common adverse effects of flibanserin, such as headaches and hypotension, occurred at similar rates regardless of alcohol consumption, indicating that the timing of flibanserin dosing may mitigate risks associated with alcohol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Evening Ethanol Consumption and Bedtime Administration of Flibanserin in Healthy Premenopausal Female Subjects. Millheiser, L., Clayton, AH., Parish, SJ., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Frequent Adverse Drug Reactions, and Medication Groups under Suspicion. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in phase one studies: a study in 430 healthy volunteers. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Evaluating the reporting of adverse events in controlled clinical trials conducted in 2010-2015 on migraine drug treatments. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Implications of the BIA-102474-101 study for review of first-into-human clinical trials. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Evening Ethanol Consumption and Bedtime Administration of Flibanserin in Healthy Premenopausal Female Subjects. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Norfenefrine in the treatment of female urinary stress incontinence assessed by one-hour pad weighing test. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical and urodynamic effects of norfenefrine in women with stress incontinence. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Trial of an alpha-adrenolytic drug (indoramin) for nocturnal enuresis. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Venlafaxine: a heterocyclic antidepressant. [2022]