Pulmonary Arterial Hypertension, Pulmonary Arterial Hypertension PAH, Pulmonary Arterial Hypertension (PAH), Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH), Pulmonary Arterial Hypertension WHO Group I
Conditions
Keywords
PAH, Pulmonary Arterial Hypertension
Brief summary
This study evaluates the effects of VI-0106 (an extended-release formulation of tacrolimus) in participants with pulmonary arterial hypertension (PAH) who continue to have functional limitations despite being on optimized background PAH therapy. Participants will be randomly assigned with equal chance to receive either VI-0106 or placebo in a double-blind fashion to assess whether VI-0106 improves outcomes in this population.
Interventions
DRUGVI-0106
Tacrolimus Extended-Release Capsules
DRUGPlacebo
Inactive oral capsule
Sponsors
VIVUS LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* WHO Group 1 PH: Pulmonary Arterial Hypertension; * WHO functional class II - IV despite optimized treatment with one or more modalities. Treatments for PAH must be stable for at least 3 months at the time of screening; * Right heart catheterization (RHC) at screening (or within 3 months prior to screening); * Screening 6MWD \>75 meters to ≤450 meters.
Exclusion criteria
* PAH due to pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis * Chronic thromboembolic or portopulmonary hypertension * Total Lung Capacity (TLC) \<60% predicted; * FEV1/FVC \<70% predicted or FEV1 \<60% predicted; * Evidence of left-sided heart disease; * Inability to safely attempt completion of the 6MWD; * Life expectancy \<6 months; * eGFR \<30 mL/min/1.73 m2 (CKD-EPI equation); * Moderate to severe hepatic dysfunction (Child-Pugh score \>10); * Serum potassium \>5.1 mEq/L; * Use of experimental PAH treatments within the past 3 months; * Active infection requiring antibiotic, antifungal, or antiviral therapies; * Current systemic treatment with cyclosporine; * Known allergy or hypersensitivity to tacrolimus; * Significant psychiatric, addictive, or other disorder that compromises the subject's ability to provide informed consent, follow study protocol, or adhere to study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in 6MWD (6 Minute Walk Distance) at Week 24 | Baseline to Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of subjects with a ≥1 category improvement vs baseline in WHO functional class at Week 24 | Baseline to Week 24 | — |
| Time to clinical worsening defined as a composite of the following events: | Baseline to Week 52 | * All-cause death; * In-patient hospitalization for PAH or right-sided heart failure; * Worsening-related placement on a recipient list for heart-lung or lung transplantation; * Diminished functional capacity (decrease from baseline 6MWD of ≥15% with an absolute value of at least 22 meters and a ≥1 category worsening of WHO functional class); * Worsening-related need to initiate rescue therapy with an approved PAH therapy, or the need to increase the dose of an IV prostacyclin infusion by 10% or more. |
| Time to clinical worsening by a restricted definition comprised of all-cause death and in-patient hospitalization for PAH or right-sided heart failure | Baseline to Week 52 | — |
| Change from baseline in 6MWD at Week 28 | Baseline to Week 28 | — |
Contacts
CONTACTVIVUS Clinical
Outcome results
None listed