A Phase 3 Study of Extended-release Tacrolimus in Subjects With Pulmonary Arterial Hypertension and Functional Limitations (TRANSCEND)

A Randomized, Double-blind, Placebo-controlled, Safety and Efficacy Study of VI-0106 (Extended-release Tacrolimus) in Subjects With PAH and Functional Limitations Despite Optimized Treatment With Available PAH Medications

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Arterial Hypertension; Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH); Pulmonary Arterial Hypertension (PAH); Pulmonary Arterial Hypertension WHO Group I; Pulmonary Arterial Hypertension PAH
• Intervention / Treatment: Drug: Placebo; Drug: VI-0106

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: VIVUS Clinical; Phone Number: 650-934-5200; Email: clinical@vivus.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VI-0106; Extended-release tacrolimus dosages of 1.25 mg or 0.625 mg oral capsules; once daily; Week 0-24, Week 28-52 during double-blind treatment period; Week 52-104 during open-label treatment period.	Drug: VI-0106; Tacrolimus Extended-Release Capsules; Other Names: Tacrolimus
Placebo Comparator: Placebo; Placebo oral capsule; once daily; Week 0-52 during double-blind treatment period.	Drug: Placebo; Inactive oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in 6MWD (6 Minute Walk Distance) at Week 24	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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:	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.	Baseline to Week 52
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

Collaborators and Investigators

• Sponsor: VIVUS LLC

Study record dates

Study Major Dates

• Study Start (Estimated): May 29, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): November 30, 2029

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: May 22, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pulmonary Arterial Hypertension; PAH
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Organic Chemicals; Macrolides; Lactones; Tacrolimus
• Other Study ID Numbers: PH-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No