Phase 2
Completed N=23
FK506 (Tacrolimus) in Pulmonary Arterial Hypertension
Source: ClinicalTrials.gov NCT01647945 ↗Enrolled (actual)
23
Serious AEs
4.4%
Results posted
Oct 2016
Primary outcomePrimary: Safety of Low-dose FK-506 in PAH — 8; 18; 9; 22 number of AEs
Summary
Mutations in bone morphogenetic protein receptor 2 (BMPR2) are present in >80% of familial and ~20% of sporadic pulmonary arterial hypertension (PAH) patients. Furthermore dysfunctional BMP signaling is a general feature of pulmonary hypertension even in non-familial PAH.
We therefore hypothesized that increasing BMP signaling might prevent and reverse the disease. We screened > 3500 FDA approved drugs for their propensity to increase BMP signaling and found FK506 (Tacrolimus) to be a strong activator of BMP signaling. Tacrolimus restored normal function of pulmonary artery endothelial cells, prevented and reversed experimental PAH in mice and rats.
Given that Tacrolimus is already FDA approved with a known side-effect profile, it is an ideal candidate drug to use in patients with pulmonary arterial hypertension.
The aims of our trial are:
1. Establish the Safety of FK506 in patients with PAH.
2. Evaluate the Efficacy of FK506 in PAH
3. Identify ideal candidates for future FK506 phase III clinical trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Safety of Low-dose FK-506 in PAH |
8; 18; 9; 22 | — |
| SECONDARY Number of Combined Clinical Events |
0; 0; 0; 0 | — |
| SECONDARY Efficacy of Low-dose FK-506 in Pulmonary Arterial Hypertension (PAH) Measured by Change in 6-min Walk Distance (6MWD) |
14.5; 0; 41; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Age ≥ 18 and 160 mm or DBP > 100mm
- Severe hypotension: SBP 10.
- Hyperkalemia defined as Potassium > 5.1 mEq/L at screening .
- Known active infection requiring antibiotic, antifungal, or antiviral therapies.
- Co-morbid conditions that would impair a patient's exercise performance and ability to assess WHO functional class, including but not limited to chronic low-back pain or peripheral musculoskeletal problems.
Data sourced from ClinicalTrials.gov (NCT01647945). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.