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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02279160




Registration number
NCT02279160
Ethics application status
Date submitted
25/10/2014
Date registered
30/10/2014
Date last updated
14/07/2020

Titles & IDs
Public title
Safety and Efficacy of APD811 in Pulmonary Arterial Hypertension
Scientific title
A Randomized, Double-blind, Parallel-group, Placebo-controlled Phase 2 Trial of Ralinepag, an Oral IP Receptor Agonist, in Patients With Pulmonary Arterial Hypertension
Secondary ID [1] 0 0
APD811-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APD811
Treatment: Drugs - Placebo

Experimental: APD811 - Multiple dose titration to maximum tolerated dose.

Placebo Comparator: Placebo - Multiple dose titration to maximum tolerated dose.


Treatment: Drugs: APD811


Treatment: Drugs: Placebo
Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Pulmonary Vascular Resistance (PVR)
Timepoint [1] 0 0
Baseline and 22 Weeks
Primary outcome [2] 0 0
Change From Baseline in 6-minute Walk Distance (6MWD) in Patients With PAH
Timepoint [2] 0 0
Baseline and 22 Weeks

Eligibility
Key inclusion criteria
- Males or females aged 18-75 years, inclusive

- Symptomatic WHO Group 1 PAH classified by one of the following subgroups:

- Idiopathic pulmonary arterial hypertension (IPAH);

- Heritable pulmonary arterial hypertension (HPAH);

- Drugs and toxins induced;

- Associated pulmonary arterial hypertension (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 and on stable oral disease-specific PAH therapy with
either an ERA and/or an agent acting on the nitric oxide pathway, i.e. a PDE5
inhibitor or a soluble guanylate 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 different 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 this study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2017
Sample size
Target
Accrual to date
Final
61
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [3] 0 0
St Vincent's Hospital - Fitzroy
Recruitment hospital [4] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
4032 - Chermside
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Bulgaria
State/province [9] 0 0
Sofia
Country [10] 0 0
Czechia
State/province [10] 0 0
Prague
Country [11] 0 0
Hungary
State/province [11] 0 0
Budapest
Country [12] 0 0
Hungary
State/province [12] 0 0
Pecs
Country [13] 0 0
Poland
State/province [13] 0 0
Bialystok
Country [14] 0 0
Poland
State/province [14] 0 0
Krakow
Country [15] 0 0
Poland
State/province [15] 0 0
Lodz
Country [16] 0 0
Romania
State/province [16] 0 0
Bucharest
Country [17] 0 0
Romania
State/province [17] 0 0
Timisoara
Country [18] 0 0
Serbia
State/province [18] 0 0
Belgrade
Country [19] 0 0
Serbia
State/province [19] 0 0
Sremska Kamenica
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
United Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The study was conducted as a placebo-controlled, randomized, 22-week double-blind study which
included a dose titration period. An additional transition period occurred for those patients
who elected to enroll into the open-label extension study, APD811-007. A total of 61 patients
with PAH were enrolled.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02279160
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Derek Solum, PhD
Address 0 0
United Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries