Trial Outcomes & Findings for FK506 (Tacrolimus) in Pulmonary Arterial Hypertension (NCT NCT01647945)

NCT ID: NCT01647945

Last Updated: 2016-10-05

Results Overview

Total number of adverse events measured between baseline and end of study at 18 weeks as reported by study subjects such as nausea/diarrhea, URI, sinus congestion, infection, fluid retention/edema, cough, headache, bronchitis, fatigue, drug reaction/hives, flushing, anxiety, tremor, fever, shingles, SOB, insomnia, pain

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 23 participants
• Primary outcome timeframe: 18 weeks
• Results posted on: 2016-10-05

Participant Flow

Participant milestones

Measure	Placebo Placebo: placebo pill	FK506 Level < 2 FK506 level \< 2 ng/ml: FK506 goal trough blood level \< 2 ng/ml	FK506 Level 2-3 FK506 level 2-3 ng/ml: FK506 goal trough blood level 2-3 ng/ml	FK506 Level 3-5 FK506 level 3-5 ng/ml: FK506 goal trough blood level 3-5 ng/ml
Overall Study STARTED	6	6	5	6
Overall Study COMPLETED	6	6	3	5
Overall Study NOT COMPLETED	0	0	2	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

FK506 (Tacrolimus) in Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Measure	Placebo n=6 Participants Placebo: placebo pill	FK506 Level < 2 n=6 Participants FK506 level \< 2 ng/ml: FK506 goal trough blood level \< 2 ng/ml	FK506 Level 2-3 n=5 Participants FK506 level 2-3 ng/ml: FK506 goal trough blood level 2-3 ng/ml	FK506 Level 3-5 n=6 Participants FK506 level 3-5 ng/ml: FK506 goal trough blood level 3-5 ng/ml	Total n=23 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	23 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	46 years n=5 Participants	35 years n=7 Participants	39 years n=5 Participants	45 years n=4 Participants	41 years n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	16 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	7 Participants n=21 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	6 participants n=4 Participants	23 participants n=21 Participants

PRIMARY outcome

Timeframe: 18 weeks

Population: all study subjects who started the study

Total number of adverse events measured between baseline and end of study at 18 weeks as reported by study subjects such as nausea/diarrhea, URI, sinus congestion, infection, fluid retention/edema, cough, headache, bronchitis, fatigue, drug reaction/hives, flushing, anxiety, tremor, fever, shingles, SOB, insomnia, pain

Outcome measures

Measure	Placebo n=6 Participants Placebo: placebo pill	FK506 Level < 2 n=6 Participants FK506 level \< 2 ng/ml: FK506 goal trough blood level \< 2 ng/ml	FK506 Level 2-3 n=5 Participants FK506 level 2-3 ng/ml: FK506 goal trough blood level 2-3 ng/ml	FK506 Level 3-5 n=6 Participants FK506 level 3-5 ng/ml: FK506 goal trough blood level 3-5 ng/ml
Safety of Low-dose FK-506 in PAH	8 number of AEs	18 number of AEs	9 number of AEs	22 number of AEs

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: Subjects were included who finished the 16 week study period. A total of 3 participants did not complete the study

Combined Clinical Events @ 16 weeks:

Number of patients who died Number of patients who got transplanted Number of patients who needed escalation of therapies Number of patients who had worsening of NYHA/WHO classification by at least 1 point Number of patients who require hospitalization for right heart failure

Low numbers would suggest either efficacy of the study drug or slowly progression of disease that is studied during the 16 week study period or short observation period or small study population

Outcome measures

Measure	Placebo n=6 Participants Placebo: placebo pill	FK506 Level < 2 n=6 Participants FK506 level \< 2 ng/ml: FK506 goal trough blood level \< 2 ng/ml	FK506 Level 2-3 n=3 Participants FK506 level 2-3 ng/ml: FK506 goal trough blood level 2-3 ng/ml	FK506 Level 3-5 n=5 Participants FK506 level 3-5 ng/ml: FK506 goal trough blood level 3-5 ng/ml
Number of Combined Clinical Events	0 Combined Number of Clinical Events	0 Combined Number of Clinical Events	0 Combined Number of Clinical Events	0 Combined Number of Clinical Events

SECONDARY outcome

Timeframe: baseline to 16 weeks

Population: Only subjects were included who finished the 16-week study 3 patients did not finish

Change in 6MWD in meter between baseline and 16 weeks

A large number would indicate an increase in exercise capacity

Outcome measures

Measure	Placebo n=6 Participants Placebo: placebo pill	FK506 Level < 2 n=6 Participants FK506 level \< 2 ng/ml: FK506 goal trough blood level \< 2 ng/ml	FK506 Level 2-3 n=3 Participants FK506 level 2-3 ng/ml: FK506 goal trough blood level 2-3 ng/ml	FK506 Level 3-5 n=5 Participants FK506 level 3-5 ng/ml: FK506 goal trough blood level 3-5 ng/ml
Efficacy of Low-dose FK-506 in Pulmonary Arterial Hypertension (PAH) Measured by Change in 6-min Walk Distance (6MWD)	14.5 meter Interval 3.5 to 38.25	0 meter Interval -20.25 to 3.0	41 meter Interval -9.5 to 59.0	0 meter Interval -20.0 to 9.0

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

FK506 Level < 2

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

FK506 Level 2-3

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

FK506 Level 3-5

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=6 participants at risk Placebo: placebo pill	FK506 Level < 2 n=6 participants at risk FK506 level \< 2 ng/ml: FK506 goal trough blood level \< 2 ng/ml	FK506 Level 2-3 n=5 participants at risk FK506 level 2-3 ng/ml: FK506 goal trough blood level 2-3 ng/ml	FK506 Level 3-5 n=6 participants at risk FK506 level 3-5 ng/ml: FK506 goal trough blood level 3-5 ng/ml
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.00% 0/6 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	16.7% 1/6 • Number of events 1 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	0.00% 0/5 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	0.00% 0/6 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.

Other adverse events

Measure	Placebo n=6 participants at risk Placebo: placebo pill	FK506 Level < 2 n=6 participants at risk FK506 level \< 2 ng/ml: FK506 goal trough blood level \< 2 ng/ml	FK506 Level 2-3 n=5 participants at risk FK506 level 2-3 ng/ml: FK506 goal trough blood level 2-3 ng/ml	FK506 Level 3-5 n=6 participants at risk FK506 level 3-5 ng/ml: FK506 goal trough blood level 3-5 ng/ml
Gastrointestinal disorders Nausea/ Diarrhea	16.7% 1/6 • Number of events 1 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	0.00% 0/6 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	60.0% 3/5 • Number of events 3 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	83.3% 5/6 • Number of events 6 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.
Respiratory, thoracic and mediastinal disorders upper respiratory tract infection	16.7% 1/6 • Number of events 1 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	33.3% 2/6 • Number of events 4 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	0.00% 0/5 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	16.7% 1/6 • Number of events 1 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.
General disorders Sinus congestion	33.3% 2/6 • Number of events 2 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	50.0% 3/6 • Number of events 4 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	0.00% 0/5 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	0.00% 0/6 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.
General disorders Fatigue	0.00% 0/6 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	0.00% 0/6 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	20.0% 1/5 • Number of events 1 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	16.7% 1/6 • Number of events 1 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.
Cardiac disorders Fluid retention	0.00% 0/6 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	16.7% 1/6 • Number of events 1 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	0.00% 0/5 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.	50.0% 3/6 • Number of events 4 • Adverse events were collected from every study subject who started the study regardless whether the subject finished the study. Events were collected during the time frame between baseline and 18 weeks. Of note the study drug was stopped at 16 weeks, an additional observation period of 2 weeks was used to capture possible adverse events of study drug.

Additional Information

Dr. Edda Spiekerkoetter

Stanford University

Phone: 650-724-1493

Email: eddas@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place