A study to investigate the safety of APD811 (study drug) and to determine the most effective dose of APD811 in patients with pulmonary arterial hypertension.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2014-000667-40-CZ
• Date of registration: 14/01/2015
• Prospective Registration: Yes
• Primary sponsor: Arena Pharmaceuticals, Inc.
• Public title: A study to investigate the safety of APD811 (study drug) and to determine the most effective dose of APD811 in patients with pulmonary arterial hypertension.
• Scientific title: A Randomized, Double-blind, Parallel-group, Placebo-controlled Phase 2 Trial of APD811, an Oral IP Receptor Agonist, in Patients with Pulmonary Arterial Hypertension
• Date of first enrolment: 23/04/2015
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000667-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Bulgaria, Czech Republic, Hungary, Poland, Romania, Serbia, Slovakia, Spain, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Arena Pharmaceuticals Inc.

• Name: Clinical Trial Information Desk
• Affiliation: Arena Pharmaceuticals Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
-Males or females aged 18-75 years, inclusive
-Symptomatic WHO Group 1 PAH classified by one of the following subgroups:
*Idiopathic PAH (IPAH)
*Heritable PAH (HPAH)
*Drugs and toxins induced
*Associated with PAH (APAH); specifically connective tissue diseases, HIV infection and congenital heart disease
-Has had the diagnosis of PAH confirmed by cardiac catheterization
-Has WHO/NYHA functional class II-IV symptomatology
-Previously diagnosed with PAH on stable oral disease-specific PAH therapy with either an ERA and/or an agent acting on the nitric oxide pathway, i.e. a PDE-5 inhibitor or a soluble guanlyate cyclase stimulator. Stable is defined as no change in dose within 3 months of the start of Screening and for the duration of the study
-Has 6MWT distances of 100-500 m, and within 15% of each other on 2 consecutive tests done on differnt days at Screening
-Has pulmonary function tests (PFTs) within 6 months prior to the start of Screening with no evidence of significant parenchymal lung disease
-Has a ventilation-perfusion (V/Q) lung scan or pulmonary angiogram within 5 years prior to Screening and concomitant with or following diagnosis of PAH that shows no evidence of thromboembolic disease
-If on vasodilators (including calcium channel blockers), digoxin, spironolactone, or L-Arginine supplementation; the patient must be on a stable dose for at least 1 month prior to the start of Screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 48
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion criteria:
-Newly diagnosed with PAH and on no disease-specific PAH therapy
-Previous participation in any clinical study with an investigational drug, biologic, or device within 2 months prior to the Screening visit
-Acutely decompensated heart failure within 1 month prior to start of Screening
-Systolic blood pressure <90 mm Hg at Screening
-Evidence or history of left-sided heart disease and/or clinically significant cardiac disease
-Use or chronic administration (defined as >30 days) of a prostacyclin or prostacyclin analogue within 3 months of Screening
-Any previous use of a prostacyclin or prostacyclin analogue that was stopped for safety or tolerability issues associated with pharmacology/mechanism of action
-Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into the study


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Pulmonary Arterial Hypertension
MedDRA version: 18.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Code: APD811
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ralinepag
CAS Number: 1187856-49-0
Current Sponsor code: APD811
Other descriptive name: AR392830
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.01-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Code: APD811
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ralinepag
CAS Number: 1187856-49-0
Current Sponsor code: APD811
Other descriptive name: AR392830
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.02-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Code: APD811
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ralinepag
CAS Number: 1187856-49-0
Current Sponsor code: APD811
Other descriptive name: AR392830
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.03-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Code: APD811
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ralinepag
CAS Number: 1187856-49-0
Current Sponsor code: APD811
Other descriptive name: AR392830
Concentration unit: mg milligram(s)
Concentration type: equal

Primary Outcome(s)

Primary end point(s): Efficacy Endpoints:
Efficacy will be assessed by measurement of pulmonary vascular resistance (PVR) obtained on RHC, measurement of B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and six-minute walk test (6MWT).

*Change from baseline in PVR
*Change from baseline in 6MWD

Secondary Objective: The secondary objecives of the study are:
-To assess the safety and tolerability of APD811
-To assess the effect of APD811 in clinical worsening

Exploratory objectes of the study are:
-To assess the effect of APD811 on levels of BNP and NT-proBNP after22 weeks of treatment
-To assess change in WHO/NYHA functional class
-To evaluate the pharmacokinetics (Cmin and presumptive Cmax) of oral APD811
-To evaluate the effects of APD811 on systemic vascular resistance (SVR)

Timepoint(s) of evaluation of this end point: Measurement of pulmonary vascular resistance (PVR) obtained on right heart catheterization (RHC)
At Screening and at End Of Study Visit


6MWT
Two 6MWTs are required during Screening and each test must be performed on a separate day
At day 35 of the Dose Titration Period
On Day 70/Week 10, Day 98/Week 14, Day 126/Week 18 of the Treatment Period and at the End Of Study Visit (EOS) (Day 154/Week 22)
Plus at the Follow-up Visit (Start of OLE) (Day 175/Week 25)

Main Objective: The primary objective of the study is to assess the hemodynamic effects of APD811 and the effect of APD811 on 6MWD in patients with PAH after 22 weeks of treatment including an initial dose titration period of up to 9 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Measurement of B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptie (NT-proBNP) levels
At day 1 of Dose Titration Period
Study Day 70/Study Week 10 of the Treatment Perid and at End Of Study Visit (Day 154/Week 22)
Plus at the Follow-up Visit (start of OLE) (Day 175/Week 25)
Assessment of clinical worsening at each study visit

Secondary end point(s): Secondary:
*Percent change from baseline in PVR
*Proportion of subjects who exhibit clinical worsening

Exploratory:
*Change from baseline in BNP/NT-proBNP
*Change from baseline in WHO/NYHA functional class
*Change from baseline in other hemodynamic parameters (e.g. SVR)

Secondary ID(s)

APD811-003

NCT02279160

Source(s) of Monetary Support

Arena Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date:
Contact: