A Study of RVT-1201 in Patients With Pulmonary Arterial Hypertension (ELEVATE 1)

Pulmonary Arterial Hypertension Clinical Trial

Official title:

A Phase 2a, Double-Blind, Placebo-Controlled Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of RVT-1201 in Patients With Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03924154
• Other study ID #: RVT-1201-2001
• Status: Terminated
• Phase: Phase 2
• Start date: August 1, 2019
• Est. completion date: February 24, 2020

Study information

• Verified date: August 2019
• Source: Altavant Sciences GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an exploratory Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of RVT-1201 in patients with pulmonary arterial hypertension (PAH).

Description:

This is an exploratory Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of RVT-1201 in patients with pulmonary arterial hypertension (PAH).

Study participation for each patient will last approximately 3 months and will consist of a screening period (up to 28 days in duration), a baseline period (day 1, pre-dose), a 6-week treatment period, and a 2-week follow-up period.

The study will enroll approximately 36 patients at approximately 20 centers across the United States and Canada.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: February 24, 2020
• Est. primary completion date: February 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

• Symptomatic PAH belonging to one of the following types:

• Idiopathic

• Heritable

• Drug- or toxin- induced

• Associated with one of the following: connective tissue disease or congenital heart disease

• World Health Organization (WHO) Functional Class (FC) II or III

• PAH diagnosed by right heart cardiac catheterization prior to Screening

• Receiving standard of care treatment for PAH with oral monotherapy or dual therapy for at least 12 weeks prior to Screening at a dose which has been stable for at least 8 weeks prior to Screening

• If on a diuretic, dose must be stable for at least 4 weeks prior to Screening, with no changes anticipated during study participation

• 6-Minute Walk Distance (6MWD) between 150 and 500 meters at Screening and Baseline visits

• Plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) level = 300 pg/mL at Screening

• Ability and willingness to give written informed consent and to comply with the requirements of the study

Key Exclusion Criteria:

• PAH associated with human immunodeficiency virus (HIV) infection, portal hypertension or schistosomiasis

• Other types of pulmonary hypertension (PH):

• Pulmonary hypertension due to left heart disease (WHO PH Group 2)

• Pulmonary hypertension due to lung diseases and/or hypoxia (WHO PH Group 3)

• Chronic thromboembolic pulmonary hypertension (WHO PH Group 4)

• Pulmonary hypertension with unclear multifactorial mechanisms (WHO PH Group 5)

• Hospitalization for pulmonary hypertension within 12 weeks of screening

• Cardiopulmonary rehabilitation program based on exercise (planned, or started = 12 weeks prior to Screening)

• Prostanoid or prostacyclin receptor agonist therapy within 12 weeks of screening

• Evidence of left-sided heart disease

• If Pulmonary function tests were done prior to screening, Pulmonary function tests demonstrate obstructive or restrictive lung disease

• Use of telotristat (Xermelo®) within the last 6 months

• Use of any investigational drug within 30 days or five half-lives (whichever is longer) prior to Screening, or 90 days if an investigational drug for PAH

• Have uncontrolled atrial fibrillation (AFib) or other uncontrolled arrhythmias

• Body mass index (BMI) >45 kg/m2

• Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• RVT-1201
RVT-1201 600 mg immediate-release tablet
• Placebo
Inactive pill manufactured to mimic RVT-1201 600 mg immediate-release tablet

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
United States	University of Colorado	Aurora	Colorado
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Pulmonary Research Institute of Southeast Michigan	Farmington Hills	Michigan
United States	University of Florida	Gainesville	Florida
United States	University of Texas Health Science Center at Houston, McGovern Medical School	Houston	Texas
United States	Kentuckiana Pulmonary Research Center	Louisville	Kentucky
United States	San Marcus Research Clinic, Inc.	Miami Lakes	Florida
United States	Louisiana State University Health Sciences Center	New Orleans	Louisiana
United States	Central Florida Pulmonary Group, P.A.	Orlando	Florida
United States	Pulmonary Associates, PA	Phoenix	Arizona
United States	Oregon Health & Science University	Portland	Oregon
United States	University of California Davis Medical Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	SBPA Research LLC	Santa Barbara	California
United States	Baystate Medical Center	Springfield	Massachusetts
United States	George Washington Medical Faculty Associates - Pulmonary Hypertension Program	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Altavant Sciences GmbH	Altavant Sciences, Inc., PPD

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events (AEs) and discontinuations due to AEs	Incidence of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and discontinuations due to AEs	8 weeks
Secondary	Concentration of biomarkers of serotonin biosynthesis in plasma	Absolute concentrations and percent change from baseline in plasma 5-hydroxyindoleacetic acid (5-HIAA) and plasma 5-hydroxytryptamine (5-HT, also known as serotonin) concentrations	8 weeks
Secondary	Concentration of biomarkers of serotonin biosynthesis in urine	Concentration of urine 5-hydroxyindoleacetic acid (5-HIAA) will be normalized against urine creatinine concentration to determine absolute ratio and percent change from baseline in urine 5-HIAA:creatinine ratio	8 weeks
Secondary	Study drug (RVT-1201) and active metabolite (KAR5417) plasma concentrations	Measured RVT-1201 and KAR5417 plasma concentrations from sparse sampling	6 weeks
Secondary	Area under the plasma concentration versus time curve (AUC) of KAR5417 (the active metabolite of RVT-1201)	Measured KAR5417 plasma concentrations from sparse sampling will be used to assess the pharmacokinetic (PK) parameter AUC of KAR5417 administered twice daily in patients with PAH, by means of population PK (PopPK) analysis	6 weeks
Secondary	Relationship between KAR5417 exposure and percent change from baseline in plasma concentrations of the serotonin-related biomarkers	Evaluate the relationship between exposure (area under the plasma concentration versus time curve [AUC]) of KAR5417 (the active metabolite of RVT-1201) and percent change from baseline in plasma concentrations of the serotonin-related biomarkers (5-HIAA and 5-HT)	6 weeks
Secondary	Relationship between KAR5417 exposure and percent change from baseline in urine concentrations of the serotonin-related biomarkers	Evaluate the relationship between exposure (area under the plasma concentration versus time curve [AUC]) of KAR5417 (the active metabolite of RVT-1201) and percent change from baseline in urine 5-HIAA:creatinine concentration ratio	6 weeks

External Links

•   RVT-1201-2001 (ELEVATE 1) study website