- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05065359
Multiple-Ascending Dose in Japanese Patients Bridging Study
July 11, 2022 updated by: Altavant Sciences GmbH
A Randomized, Double-Blinded, Placebo-Controlled, MultipleAscending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Rodatristat Ethyl in Healthy Japanese and Caucasian Subjects
This study is a randomized, placebo-controlled, multiple-ascending dose study in healthy Japanese and Caucasian subjects.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This study is a randomized, placebo-controlled, multiple-ascending dose study in healthy Japanese and Caucasian subjects.
Two dose levels of rodatristat ethyl, 300 mg twice daily (BID) and 600 mg BID multiple doses (with a single dose lead in), will be explored in an ascending dose fashion with a safety review in between (Figure 1 below).
Approximately 48 subjects will be enrolled in 4 cohorts.
Study Type
Interventional
Enrollment (Actual)
47
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
Glendale, California, United States, 91206
- California Clinical Trials Medical Group (CCTMG)
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Healthy males or females aged 18 to 55 years, inclusive
- 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 starting at Screening, during the treatment period, and for at least 100 days after the last dose of Investigational Product (IP), and refrain from donating sperm during this period.
- Female subjects of childbearing potential must agree to use contraception starting at Screening, during the treatment period, and for at least 30 days after the last dose of IP.
- Body mass index (BMI) ≥ 18 kg/m2 and ≤ 32 kg/m2 at Screening
- Japanese subjects must have been born in Japan and not have lived outside of Japan > 10 years at the time of Screening, have both parents and grandparents of ethnic Japanese origin, and have not significantly modified their diets since leaving Japan.
- Caucasian subjects must be of European or Latin American descent (i.e., White).
- Capable of giving signed informed consent, able to understand and comply with protocol requirements, instructions, and protocol related restrictions, and likely to complete the study as planned.
Exclusion Criteria:
- 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, hematologic, renal, hepatic, bronchopulmonary, neurological, psychiatric, or cardiovascular disease
- a. History of Gilbert's Syndrome
- b. History of depression
- c. History of any allergy that, in the opinion of the Investigator, contraindicates participation in the trial
- Any positive finding on the Columbia-Suicide Severity Rating Scale (C-SSRS).
- Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at Screening) of 50 mL to 499 mL of blood within 30 days or more than 499 mL within 56 days prior to Day 1
- Participation in an investigational drug, vaccine, or device study within 30 days before IP administration or 90 days for a biologic study
- Evidence of previous myocardial infarction
- a. Any conduction abnormality (including but not specific to atrioventricular block [2nd degree or higher], Wolff Parkinson White syndrome [unless curative ablation treatment]).
- b. Sinus pauses > 3 seconds.
- c. Any significant arrhythmia which, in the opinion of the Investigator and Medical Monitor, will interfere with the safety for the individual subject.
- d. Non-sustained or sustained ventricular tachycardia (≥ 3 consecutive ventricular ectopic beats).
- Abnormal blood pressure, either low (defined as < 90 mmHg systolic and/or < 50 mmHg diastolic) or high (defined as > 140 mmHg systolic and/or > 90 mmHg diastolic)
- Clinically significant abnormalities in laboratory test results (including hepatic and renal panels, complete blood count, coagulation, chemistry panel, and urinalysis)
- a. Positive serology for hepatitis B, hepatitis C virus, or human immunodeficiency virus
- b. Estimated glomerular filtration rate < 80 mL/min/1.73 m2
- c. Aspartate aminotransferase, alanine aminotransferase values greater than 1.5 x upper limit of normal.
- d. Positive urine test for drugs of abuse
- e. Positive alcohol test (breath, saliva, or urine)
- Use of prescription or nonprescription drugs including high dose vitamins, dietary supplements (including St. John's Wort) within 7 days or 5 half-lives of the prescription or nonprescription drug (whichever was longer) prior to the first dose of IP product, unless in the opinion of the Investigator and Sponsor, the medication would not interfere with the study outcomes or compromise subject safety.
- Subject unable to abstain from consumption of tryptophan-rich foods 48 hours prior to admission to the clinic through the Follow-up visit
- Consumption of grapefruit or Seville oranges or their juices within the 7 days prior to dosing until collection of the final PK sample.
- Use of medications associated with QT prolongation within 30 days prior to dosing and during the study. A list of prohibited medications is provided in an appendix to the protocol.
- Subjects unable to abstain from alcohol for 72 hours prior to the start of dosing through collection of their final PK sample
- Subjects with a clinical history of or current alcohol abuse defined as an average weekly intake of more than 21 units for males or 15 units for females (1 unit = 340 mL beer, 115 mL wine, or 43 mL spirits).
- Subjects with a clinical history of or current illicit drug use which, in the opinion of the Investigator, would interfere with the subject's ability to complete the study and could compromise subject safety and/or the results of the study.
- Subjects unable to abstain from caffeine, xanthine, or strenuous exercise for 72 hours prior to dosing until collection of their final PK sample.
- Subjects who have smoked or used tobacco or nicotine-containing products or cannabidiol and related products (in all forms) within 3 months prior to the Screening visit and who are unwilling to refrain from cannabidiol and related products, smoking, tobacco use, or use of nicotine products and all for the entire duration of the study (through the Follow-up visit)
- History of hypersensitivity to rodatristat ethyl, any its components, or any components in the placebo preparation.
- Employed as site personnel directly involved with this study
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Rodatristat Ethyl 300 mg BID - Japanese subjects
|
Tablets, oral, 300 mg, BID 14 days
|
Placebo Comparator: Placebo match for Rodatristat Ethyl 300 mg BID - Japanese subjects
|
Tablets, oral, 0 mg, BID for 14 days
|
Experimental: Rodatristat Ethyl 300 mg BID - Caucasian subjects
|
Tablets, oral, 300 mg, BID 14 days
|
Placebo Comparator: Placebo match for Rodatristat Ethyl 300 mg BID - Caucasian subjects
|
Tablets, oral, 0 mg, BID for 14 days
|
Experimental: Rodatristat Ethyl 600 mg BID - Japanese subjects
|
Tablets, oral, 600 mg, BID 14 days
|
Placebo Comparator: Placebo match for Rodatristat Ethyl 600 mg BID - Japanese subjects
|
Tablets, oral, 0 mg, BID for 14 days
|
Experimental: Rodatristat Ethyl 600 mg BID - Caucasian subjects
|
Tablets, oral, 600 mg, BID 14 days
|
Placebo Comparator: Placebo match for Rodatristat Ethyl 600 mg BID - Caucasian subjects
|
Tablets, oral, 0 mg, BID for 14 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of rodatristat ethyl by incidence of adverse events
Time Frame: 21 days
|
Assessments of adverse events
|
21 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Single dose AUC(0-∞)
Time Frame: 21 days
|
Single dose area under the concentration time curve from time zero (predose-) extrapolated to infinity (AUC(0-∞)) of rodatristat ethyl and metabolite(s).
|
21 days
|
Single dose AUC(0-t)
Time Frame: 21 days
|
Single dose area under the concentration time curve from time zero to the last detectable time point (AUC(0-t)) of rodatristat ethyl and metabolite(s).
|
21 days
|
Single dose Cmax
Time Frame: 21 days
|
Single dose maximum observed concentration (Cmax) of rodatristat ethyl and metabolite(s).
|
21 days
|
Single dose tmax
Time Frame: 21 days
|
Single dose time to maximum concentration (tmax) of rodatristat ethyl and metabolite(s).
|
21 days
|
Single dose t½
Time Frame: 21 days
|
Single dose elimination half-life (t½) of rodatristat ethyl and metabolite(s).
|
21 days
|
Steady state tmax
Time Frame: 21 days
|
Steady-state tmax of rodatristat ethyl and metabolite(s).
|
21 days
|
Steady state Cmax
Time Frame: 21 days
|
Steady-state Cmax of rodatristat ethyl and metabolite(s).
|
21 days
|
Steady state Cτ
Time Frame: 21 days
|
Steady-state concentration at end of dosing interval (Cτ) of rodatristat ethyl and metabolite(s).
|
21 days
|
Steady state Cavg
Time Frame: 21 days
|
Steady-state average concentration at steady state (Cavg) of rodatristat ethyl and metabolite(s).
|
21 days
|
Steady state AUC(0-τ)
Time Frame: 21 days
|
Steady-state area under the concentration-time curve over the dosing interval at steady-state (AUC(0-τ)) of rodatristat ethyl and metabolite(s).
|
21 days
|
Steady state t½
Time Frame: 21 days
|
Steady-state t½ of rodatristat ethyl and metabolite(s).
|
21 days
|
Pharmacodynamic assessment - change from baseline in 5-HIAA concentrations
Time Frame: 21 days
|
PD as assessed by the change from baseline in 5-hydroxyindoleacedtic acid (5-HIAA) concentrations (plasma and 24-hour urinary excretion)
|
21 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 1, 2021
Primary Completion (Actual)
March 30, 2022
Study Completion (Actual)
March 30, 2022
Study Registration Dates
First Submitted
August 2, 2021
First Submitted That Met QC Criteria
September 22, 2021
First Posted (Actual)
October 4, 2021
Study Record Updates
Last Update Posted (Actual)
July 13, 2022
Last Update Submitted That Met QC Criteria
July 11, 2022
Last Verified
July 1, 2022
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- RVT-1201-1005
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Healthy
-
Prevent Age Resort "Pervaya Liniya"RecruitingHealthy Aging | Healthy Diet | Healthy LifestyleRussian Federation
-
Maastricht University Medical CenterCompletedHealthy Volunteers | Healthy Subjects | Healthy AdultsNetherlands
-
Yale UniversityNot yet recruitingHealth-related Benefits of Introducing Table Olives Into the Diet of Young Adults: Olives For HealthHealthy Diet | Healthy Lifestyle | Healthy Nutrition | CholesterolUnited States
-
University of PennsylvaniaActive, not recruitingHealthy | Healthy AgingUnited States
-
Chalmers University of TechnologyGöteborg UniversityCompletedHealthy | Nutrition, HealthySweden
-
Hasselt UniversityRecruitingHealthy | Healthy AgingBelgium
-
Galera Therapeutics, Inc.Syneos HealthCompleted
-
Galera Therapeutics, Inc.Syneos HealthCompletedHealthy | Healthy VolunteersAustralia
-
University of ManitobaNot yet recruitingHealthy | Healthy Diet
Clinical Trials on Rodatristat Ethyl 300 mg BID
-
Altavant Sciences GmbHCompletedPulmonary Arterial HypertensionUnited States, Spain, United Kingdom, Czechia, Serbia, Canada, Poland, Italy, Bosnia and Herzegovina, Austria, Germany, Belgium, Bulgaria, France, Latvia, Moldova, Republic of, Ukraine
-
Altavant Sciences GmbHCovance; Altavant Sciences, Inc.Completed
-
Altavant Sciences GmbHPPDCompleted
-
AstraZenecaCompletedParkinson's DiseaseUnited States
-
Innovation Pharmaceuticals, Inc.CompletedChronic Stable Plaque PsoriasisUnited States
-
Future MedicineRecruitingFM101 Efficacy Study in Adults With Nonalcoholic Fatty Liver Disease or Nonalcoholic SteatohepatitisNonalcoholic Fatty Liver Disease | Nonalcoholic SteatohepatitisSpain, Hungary, Poland
-
RFS Pharma, LLCWithdrawnHuman Immunodeficiency Virus Infection
-
Altavant Sciences GmbHPPD; Altavant Sciences, Inc.TerminatedPulmonary Arterial HypertensionUnited States, Canada
-
MedPacto, Inc.RecruitingCarcinoma, Non-Small-Cell LungKorea, Republic of
-
RFS Pharma, LLCTerminatedHuman Immunodeficiency Virus InfectionArgentina