Thorough QT Study to Evaluate the Effect of Rodatristat Ethyl, Rodatristat and Its Major Metabolites on the Heart

NCT05933447 | Completed Phase 1 FDA Drug

• 1 other identifier: RVT-1201-1004
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate whether Rodatristat Ethyl prolongs the QTc interval when orally administered to healthy volunteers.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Evaluate the effect of rodatristat ethyl, rodatristat, and its major metabolites on the Fredericia-corrected QT interval in healthy volunteers using concentration-QT analyses following administration of multiple doses of rodatristat ethyl

  Measure change in baseline in QTcF

  20 Days

Secondary Outcomes (3)

• Evaluate the effect of multiple doses of rodatristat ethyl on other electrocardiogram (ECG) parameters

  55 Days

• Evaluate the pharmacokinetics (PK) of rodatristat ethyl, rodatristat and it's major metabolites following multiple doses of rodatristat ethyl

  55 Days

• Evaluate effect of multiple doses of rodatristat ethyl on plasma 5-hydroxyindoleacetic acid (5-HIAA)

  55 Days

Study Arms (4)

Rodatristat Ethyl

EXPERIMENTAL

Drug: Rodatristat Ethyl

Moxifloxacin

ACTIVE COMPARATOR

Drug: Moxifloxacin

Placebo for Rodatristat

PLACEBO COMPARATOR

Drug: Placebo for Rodatristat

Placebo for Moxifloxacin

PLACEBO COMPARATOR

Drug: Placebo for Moxifloxacin

Interventions

Rodatristat Ethyl DRUG

Oral, Tablet, 300 mg QD, 300 mg BID, 600 mg BID, 900 mg BID, 900 mg QD

Rodatristat Ethyl

Moxifloxacin DRUG

Oral, Tablet, 400 mg QD

Moxifloxacin

Placebo for Rodatristat DRUG

Oral, Tablet, O mg QD, 0 mg BID

Placebo for Rodatristat

Placebo for Moxifloxacin DRUG

Oral, Tablet, 0 mg QD

Placebo for Moxifloxacin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to give written informed consent and to comply with the requirements of the study for its duration.
• Healthy adult males or females aged 18 to 55 years, inclusive. As determined by the Investigator, healthy subjects are defined as individuals free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, cardiac monitoring, and clinical laboratory test results.
• A male subject is eligible to participate if he does not have a female partner who is pregnant or who intends to become pregnant during the study. Male subjects must agree to use contraception.
• Female subjects of childbearing potential must agree to use contraception.
• Body mass index (BMI) within 18.0 kg/m2 to 33.0 kg/m2, inclusively.

You may not qualify if:

• Female who is lactating.
• Positive pregnancy test at the Screening visit or check-in or planning to become pregnant within the next 6 months.
• Pulse rate less than 40 beats per minute (bpm) or more than 100 bpm at the Screening visit or check-in.
• A sustained supine systolic blood pressure \> 140 mm Hg or \< 90 mmHg or a supine diastolic blood pressure \> 90 mmHg or \< 50 mmHg at the Screening visit, check-in, or prior to dosing.
• History of significant hypersensitivity to rodatristat ethyl, moxifloxacin, or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
• As determined by the Investigator, any known pre-existing medical or psychiatric condition that could interfere with the subject's ability to provide informed consent or participate in study conduct, or that may confound study findings including, but not limited to a history of clinically significant gastrointestinal (including cholecystectomy), hematologic, renal, hepatic, bronchopulmonary, neurological, psychiatric, endocrine, immunologic, dermatologic or cardiovascular disease, including:
• History of Gilbert's Syndrome
• History of depression
• History of any allergy that, in the opinion of the Investigator, contraindicates participation in the trial
• An uninterpretable or abnormal Screening ECG indicating a second or third degree atrioventricular block, presence of out-of-range cardiac interval (heart rate \[HR\] \< 40 bpm, PR \< 110 msec, PR \> 200 msec, QRS \< 60 msec, QRS \>110 msec and Fridericia-corrected QT interval (QTcF) \> 450 msec for males and \> 470 msec for females) on the ECG at the Screening visit or other clinically significant ECG abnormalities, unless deemed non significant by an investigator.
• History of risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesemia. Subjects will also be excluded if there is a family history of long QT syndrome or Brugada syndrome.
• Clinically significant abnormalities in laboratory test results, as determined by the Investigator, (including hepatic and renal panels, complete blood count, coagulation, chemistry panel, and urinalysis) at the Screening visit or check-in that are confirmed by a repeat reading .
• Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
• Estimated glomerular filtration rate \< 80 mL/min/1.73 m2 at the Screening visit, calculated using the Cockcroft-Gault formula
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) values greater than upper limit of normal (ULN). A single repeat measurement is allowed for eligibility determination

Sponsors & Collaborators

• Altavant Sciences GmbH: lead
• Altasciences Clinical Kansas, Inc.: collaborator

Study Sites (1)

Altasciences Clinical Kansas, Inc.

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Interventions

rodatristat; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Martin Kankam, MD

  Altasciences Clinical Kansas, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2023
• First Posted: July 6, 2023
• Study Start: May 12, 2023
• Primary Completion: July 28, 2023
• Study Completion: July 28, 2023
• Last Updated: October 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)