Trial Outcomes & Findings for Pharmacokinetic Study of Pitavastatin and Ritonavir-Boosted Darunavir or Efavirenz (NCT NCT01695954)

NCT ID: NCT01695954

Last Updated: 2020-08-11

Results Overview

24-hour area under the curve (AUC) for pitavastatin when coadministered with efavirenz and with darunavir/ritonavir and 24-hour AUC for efavirenz or darunavir when coadministered with pitavastatin

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 34 participants
• Primary outcome timeframe: 0 to 24 hours
• Results posted on: 2020-08-11

Participant Flow

Accrual began August 24, 2012 and ended January, 8, 2013. All study procedures took place at the NYU/Bellevue Clinical Trials Unit and NYU Clinical and Translational Science Institute.

Participant milestones

Measure	Arm A: (Pitavastatin and Efavirenz) Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.	Arm B: (Pitavastatin and Ritonavir-boosted Darunavir) Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.
Overall Study STARTED	18	16
Overall Study COMPLETED	14	14
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Measure	Arm A: (Pitavastatin and Efavirenz) Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.	Arm B: (Pitavastatin and Ritonavir-boosted Darunavir) Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.
Overall Study Withdrawal by Subject	4	0
Overall Study Adverse Event	0	2

Baseline Characteristics

Pharmacokinetic Study of Pitavastatin and Ritonavir-Boosted Darunavir or Efavirenz

Baseline characteristics by cohort

Measure	Arm A: (Pitavastatin and Efavirenz) n=18 Participants Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.	Arm B: (Pitavastatin and Ritonavir-boosted Darunavir) n=16 Participants Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.	Total n=34 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
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants	16 Participants n=7 Participants	34 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: 0 to 24 hours

Population: Subjects who completed all visits

24-hour area under the curve (AUC) for pitavastatin when coadministered with efavirenz and with darunavir/ritonavir and 24-hour AUC for efavirenz or darunavir when coadministered with pitavastatin

Outcome measures

Measure	Arm A: (Pitavastatin and Efavirenz) n=18 Participants Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime for the first 4 days, then efavirenz 600 mg at bedtime for the next 10 days and both pitavastatin 2 mg and efavirenz 600 mg at bedtime for the final 4 days. Blood will be drawn on days 0, 4, 14 and 18.	Arm B: (Pitavastatin and Darunavir) n=16 Participants Subjects in arm will receive pitavastatin 2 mg daily for the first 4 days, then darunavir 400 mg x 2 tabs and ritonavir 100 mg x 1 tab daily for the next 10 days and will receive both pitavastatin 2 mg and darunavir 400 mg x 2 tabs and ritonavir 100 mg x 1 tab daily for the final 4 days. Blood will be drawn on days 0, 4, 14, and 18.
AUC	85.3 ng*hr/mL Standard Deviation 5.72	62.8 ng*hr/mL Standard Deviation 6.24

PRIMARY outcome

Timeframe: 0 to 24 hours

Population: Subjects who completed all visits

Geometric Mean Ratio (GMR) of 24- Hour Area under the plasma drug concentration-time curve (AUC) of pitavastatin when coadministered with efavirenz or with darunavir/ritonavir over 24 Hour (AUC) of pitavastatin

Outcome measures

Measure	Arm A: (Pitavastatin and Efavirenz) n=18 Participants Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime for the first 4 days, then efavirenz 600 mg at bedtime for the next 10 days and both pitavastatin 2 mg and efavirenz 600 mg at bedtime for the final 4 days. Blood will be drawn on days 0, 4, 14 and 18.	Arm B: (Pitavastatin and Darunavir) n=16 Participants Subjects in arm will receive pitavastatin 2 mg daily for the first 4 days, then darunavir 400 mg x 2 tabs and ritonavir 100 mg x 1 tab daily for the next 10 days and will receive both pitavastatin 2 mg and darunavir 400 mg x 2 tabs and ritonavir 100 mg x 1 tab daily for the final 4 days. Blood will be drawn on days 0, 4, 14, and 18.
GMR of 24- Hour AUC of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir Over 24 Hour AUC of Pitavastatin GMR of Pitavastatin with (EFV or DRV)/Pitavastatin	.89 Ratio Interval 0.7321 to 1.09	.91 Ratio Interval 0.78 to 1.06
GMR of 24- Hour AUC of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir Over 24 Hour AUC of Pitavastatin GMR of (EFV or DRV) with Pitavastatin/(EFV or DRV)	.90 Ratio Interval 0.75 to 1.06	1.08 Ratio Interval 0.96 to 1.22

SECONDARY outcome

Timeframe: Day 18

Geometric Mean Ratio (GMR) of Cmax for pitavastatin with Efavirenz vs. alone and GMR of Cmax for pitavastatin with darunavir/ritonavir vs. alone was reported.

Outcome measures

Measure	Arm A: (Pitavastatin and Efavirenz) n=18 Participants Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime for the first 4 days, then efavirenz 600 mg at bedtime for the next 10 days and both pitavastatin 2 mg and efavirenz 600 mg at bedtime for the final 4 days. Blood will be drawn on days 0, 4, 14 and 18.	Arm B: (Pitavastatin and Darunavir) n=16 Participants Subjects in arm will receive pitavastatin 2 mg daily for the first 4 days, then darunavir 400 mg x 2 tabs and ritonavir 100 mg x 1 tab daily for the next 10 days and will receive both pitavastatin 2 mg and darunavir 400 mg x 2 tabs and ritonavir 100 mg x 1 tab daily for the final 4 days. Blood will be drawn on days 0, 4, 14, and 18.
GMR of Cmax of Pitavastatin When Coadministered With Efavirenz or With Darunavir/Ritonavir	1.20 ng/mL Interval 0.79 to 1.83	0.93 ng/mL Interval 0.72 to 1.19

Adverse Events

Arm A: (Pitavastatin and Efavirenz)

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Arm B: (Pitavastatin and Ritonavir-boosted Darunavir)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Arm A: (Pitavastatin and Efavirenz) n=18 participants at risk Subjects assigned to Arm A will receive pitavastatin 2 mg at bedtime and efavirenz 600 mg at bedtime.	Arm B: (Pitavastatin and Ritonavir-boosted Darunavir) n=16 participants at risk Subjects assigned to Arm B will receive pitavastatin 2 mg daily and darunavir 800 mg with ritonavir 100 mg daily.
Nervous system disorders Headache	11.1% 2/18 • Number of events 4 • 7 months.	6.2% 1/16 • Number of events 1 • 7 months.
Skin and subcutaneous tissue disorders Rash	5.6% 1/18 • Number of events 1 • 7 months.	12.5% 2/16 • Number of events 2 • 7 months.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	5.6% 1/18 • Number of events 2 • 7 months.	6.2% 1/16 • Number of events 1 • 7 months.
Nervous system disorders Dizziness	11.1% 2/18 • Number of events 3 • 7 months.	0.00% 0/16 • 7 months.
Nervous system disorders Nausea	11.1% 2/18 • Number of events 2 • 7 months.	0.00% 0/16 • 7 months.
Gastrointestinal disorders Vomiting	5.6% 1/18 • Number of events 1 • 7 months.	0.00% 0/16 • 7 months.
Nervous system disorders Vivid dreams	5.6% 1/18 • Number of events 2 • 7 months.	0.00% 0/16 • 7 months.
Musculoskeletal and connective tissue disorders Pain at venipuncture site	0.00% 0/18 • 7 months.	6.2% 1/16 • Number of events 1 • 7 months.
General disorders Fever	5.6% 1/18 • Number of events 1 • 7 months.	0.00% 0/16 • 7 months.
Blood and lymphatic system disorders Anemia	5.6% 1/18 • Number of events 1 • 7 months.	0.00% 0/16 • 7 months.
Blood and lymphatic system disorders Leukocytosis	5.6% 1/18 • Number of events 1 • 7 months.	0.00% 0/16 • 7 months.
General disorders CPK elevation	0.00% 0/18 • 7 months.	6.2% 1/16 • Number of events 1 • 7 months.
Gastrointestinal disorders Diarrhea	5.6% 1/18 • Number of events 1 • 7 months.	6.2% 1/16 • Number of events 1 • 7 months.

Additional Information

Carlos Malvestutto, MD, MPH

NYU School of Medicine

Phone: 212-263-3570

Email: carlos.malvestutto@nyumc.org

Results disclosure agreements

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