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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 : Not yet recruiting
First Posted : April 23, 2019
Last Update Posted : April 23, 2019
Sponsor:
Collaborators:
Altavant Sciences, Inc.
PPD
Information provided by (Responsible Party):
Altavant Sciences GmbH

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).

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: RVT-1201 Drug: Placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
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 bis in die (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 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
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
Estimated Study Start Date : April 30, 2019
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : February 28, 2020


Arm Intervention/treatment
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])
Drug: RVT-1201
RVT-1201 600 mg immediate-release tablet

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])
Drug: Placebo
Inactive pill manufactured to mimic RVT-1201 600 mg immediate-release tablet
Other Name: Placebo (for RVT-1201)




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Study drug (RVT-1201) and active metabolite (KAR5417) plasma concentrations [ Time Frame: 6 weeks ]
    Measured RVT-1201 and KAR5417 plasma concentrations from sparse sampling

  4. 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

  5. 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)

  6. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
    • 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
  • Cardio pulmonary rehabilitation program based on exercise (planned, or started ≤ 12 weeks prior to Screening)
  • Prostanoid or prostacyclin receptor agonist therapy within 12 weeks of screening
  • Use of any of the following medications within 30 days prior to Screening:

    • Narrow therapeutic range cytochrome P450 (CYP) 2C8 substrates
    • Narrow therapeutic range P-gp substrates, including digoxin
    • Monoamine oxidase inhibitors (MAOIs)
    • 5-Hydroxytryptophan (5-HTP)
  • 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
  • Heart attack or stroke within 12 weeks prior to Screening
  • Have atrial fibrillation (AFib) or other uncontrolled arrhythmias
  • Body mass index (BMI) >35
  • Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03924154


Contacts
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Contact: Julie Rurka (919) 808-4339 julie.rurka@altavant.com
Contact: Liz Mascherino (919) 808-4231 liz.mascherino@altavant.com

Locations
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United States, Florida
San Marcus Research Clinic, Inc. Not yet recruiting
Miami Lakes, Florida, United States, 33014
Principal Investigator: Belkis Delgado, MD         
Sponsors and Collaborators
Altavant Sciences GmbH
Altavant Sciences, Inc.
PPD
Investigators
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Study Director: Laurence Keller, MD Altavant Sciences, Inc.

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Responsible Party: Altavant Sciences GmbH
ClinicalTrials.gov Identifier: NCT03924154     History of Changes
Other Study ID Numbers: RVT-1201-2001
First Posted: April 23, 2019    Key Record Dates
Last Update Posted: April 23, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Altavant Sciences GmbH:
Pulmonary arterial hypertension (PAH)
Pulmonary hypertension (PH)
RVT-1201
Rodatristat ethyl
Tryptophan hydroxylase (TPH)
Serotonin reduction
ELEVATE 1
KAR5417

Additional relevant MeSH terms:
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Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases