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

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ClinicalTrials.gov Identifier: NCT03924154
Recruitment Status : Terminated (Inability to enroll)
First Posted : April 23, 2019
Last Update Posted : March 9, 2020
Sponsor:
Collaborators:
Altavant Sciences, Inc.
PPD
Information provided by (Responsible Party):
Altavant Sciences GmbH

Tracking Information
First Submitted Date  ICMJE April 5, 2019
First Posted Date  ICMJE April 23, 2019
Last Update Posted Date March 9, 2020
Actual Study Start Date  ICMJE August 1, 2019
Actual Primary Completion Date February 24, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2019)
Adverse events (AEs) and discontinuations due to AEs [ Time Frame: 8 weeks ]
Incidence of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and discontinuations due to AEs
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2019)
  • Concentration of biomarkers of serotonin biosynthesis in plasma [ Time Frame: 8 weeks ]
    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
  • Concentration of biomarkers of serotonin biosynthesis in urine [ Time Frame: 8 weeks ]
    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
  • Study drug (RVT-1201) and active metabolite (KAR5417) plasma concentrations [ Time Frame: 6 weeks ]
    Measured RVT-1201 and KAR5417 plasma concentrations from sparse sampling
  • Area under the plasma concentration versus time curve (AUC) of KAR5417 (the active metabolite of RVT-1201) [ Time Frame: 6 weeks ]
    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
  • Relationship between KAR5417 exposure and percent change from baseline in plasma concentrations of the serotonin-related biomarkers [ Time Frame: 6 weeks ]
    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)
  • Relationship between KAR5417 exposure and percent change from baseline in urine concentrations of the serotonin-related biomarkers [ Time Frame: 6 weeks ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of RVT-1201 in Patients With Pulmonary Arterial Hypertension (ELEVATE 1)
Official Title  ICMJE 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
Brief 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).
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Following screening assessments, PAH patients who meet all entrance criteria will be randomly assigned to receive one of the following treatments in a ratio of 2:1:

  • Arm 1 (n=24) - RVT-1201 Treatment: RVT-1201 immediate-release tablets will be administered orally, at a dose of 600 mg twice daily (BID), for a total of 6 weeks in addition to the patient's current standard of care (SOC) medication(s) for PAH.
  • Arm 2 (n=12) - Placebo Treatment: Matching placebo tablets will be administered orally, at a dose of 600 mg twice daily (BID), for a total of 6 weeks in addition to the patient's current SOC medication(s) for PAH.

Participants will be followed in face-to-face visits with trial personnel every 2 weeks for 8 weeks (6 weeks of treatment plus a 2-week follow-up), with an additional phone call at Week 1, to assess drug effects and monitor safety during their treatments.

Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE
  • Drug: RVT-1201
    RVT-1201 600 mg immediate-release tablet
    Other Name: rodatristat ethyl
  • Drug: Placebo
    Inactive pill manufactured to mimic RVT-1201 600 mg immediate-release tablet
    Other Name: Placebo (for RVT-1201)
Study Arms  ICMJE
  • Experimental: RVT-1201
    RVT-1201 600 mg immediate-release tablet, administered orally twice daily with food for 6 weeks, in addition to the patient's current standard of care medication(s) for PAH (n=24 [Anticipated])
    Intervention: Drug: RVT-1201
  • Placebo Comparator: Placebo
    Matching placebo tablet, administered orally twice daily with food for 6 weeks, in addition to the patient's current standard of care medication(s) for PAH (n=12 [Anticipated])
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 5, 2020)
3
Original Estimated Enrollment  ICMJE
 (submitted: April 22, 2019)
36
Actual Study Completion Date  ICMJE February 24, 2020
Actual Primary Completion Date February 24, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03924154
Other Study ID Numbers  ICMJE RVT-1201-2001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Altavant Sciences GmbH
Study Sponsor  ICMJE Altavant Sciences GmbH
Collaborators  ICMJE
  • Altavant Sciences, Inc.
  • PPD
Investigators  ICMJE
Study Director: Ed Parsley, DO Altavant Sciences
PRS Account Altavant Sciences GmbH
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP