Trial Outcomes & Findings for Darunavir/Ritonavir and Rosuvastatin Pharmacokinetic Study (NCT NCT00885495)
NCT ID: NCT00885495
Last Updated: 2022-02-11
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
17 participants
Primary outcome timeframe
7 days
Results posted on
2022-02-11
Participant Flow
Subjects were recruited from the community between September 2008 and March 2009
1 subject was excluded based upon elevated triglyceride level prior to randomization
Participant milestones
| Measure |
B-Darunavir+Ritonavir Initial Arm
Darunavir+ritonavir x 7 days; Rosuvastatin x 7 days; Combination x 7 days
|
A-Rosuvastatin Initial Arm
Rosuvastatin x 7 days; darunavir+ritonavir x 7 days; Combination x 7 days
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
9
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
B-Darunavir+Ritonavir Initial Arm
Darunavir+ritonavir x 7 days; Rosuvastatin x 7 days; Combination x 7 days
|
A-Rosuvastatin Initial Arm
Rosuvastatin x 7 days; darunavir+ritonavir x 7 days; Combination x 7 days
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
2
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Darunavir/Ritonavir and Rosuvastatin Pharmacokinetic Study
Baseline characteristics by cohort
| Measure |
B-Darunavir+Ritonavir Initial Arm
n=8 Participants
Darunavir+ritonavir x 7 days; Rosuvastatin x 7 days; Combination x 7 days
|
A-Rosuvastatin Initial Arm
n=9 Participants
Rosuvastatin x 7 days; darunavir+ritonavir x 7 days; Combination x 7 days
|
Total
n=17 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
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
28 years
STANDARD_DEVIATION 11 • n=5 Participants
|
28 years
STANDARD_DEVIATION 10 • n=7 Participants
|
28 years
STANDARD_DEVIATION 10 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
9 participants
n=7 Participants
|
17 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 7 daysPopulation: Analysis of 12 subjects who completed all 3 PK visits
Outcome measures
| Measure |
Rosuvastatin
n=12 Participants
Rosuvastatin 10 mg daily for 7 days.
|
Rosuvastatin-Darunavir-Ritonavir
n=12 Participants
Rosuvastatin 10 mg daily, Darunavir 600 mg and Ritonavir 100 mg twice daily for 7 days
|
Rosuvastatin+Darunavir/Ritonavir
LDL values with all three medications
|
|---|---|---|---|
|
Cmax of Rosuvastatin
|
6.70 ng/mL
Interval 5.26 to 8.53
|
16.32 ng/mL
Interval 11.78 to 22.61
|
—
|
PRIMARY outcome
Timeframe: 7 daysPopulation: Analysis of 12 subjects who completed all 3 PK visits
Outcome measures
| Measure |
Rosuvastatin
n=12 Participants
Rosuvastatin 10 mg daily for 7 days.
|
Rosuvastatin-Darunavir-Ritonavir
n=12 Participants
Rosuvastatin 10 mg daily, Darunavir 600 mg and Ritonavir 100 mg twice daily for 7 days
|
Rosuvastatin+Darunavir/Ritonavir
LDL values with all three medications
|
|---|---|---|---|
|
AUC of Rosuvastatin
|
108.96 ng*hr/mL
Interval 83.85 to 141.6
|
161.24 ng*hr/mL
Interval 124.62 to 208.59
|
—
|
SECONDARY outcome
Timeframe: 45 daysPopulation: Participants taking all three medications
Geometric mean of the Concentration minimum of darunavir and ritonavir in the presence and absence of rosuvastatin.
Outcome measures
| Measure |
Rosuvastatin
n=12 Participants
Rosuvastatin 10 mg daily for 7 days.
|
Rosuvastatin-Darunavir-Ritonavir
Rosuvastatin 10 mg daily, Darunavir 600 mg and Ritonavir 100 mg twice daily for 7 days
|
Rosuvastatin+Darunavir/Ritonavir
LDL values with all three medications
|
|---|---|---|---|
|
To Investigate the Effect of Rosuvastatin on the Steady State Pharmacokinetics of Darunavir/Ritonavir.
Darunavir Cmin absent Rosuvastatin
|
3235 ng/mL
Interval 2759.0 to 3794.0
|
—
|
—
|
|
To Investigate the Effect of Rosuvastatin on the Steady State Pharmacokinetics of Darunavir/Ritonavir.
Ritonavir Cmin absent Rousuvastatin
|
194 ng/mL
Interval 142.0 to 266.0
|
—
|
—
|
|
To Investigate the Effect of Rosuvastatin on the Steady State Pharmacokinetics of Darunavir/Ritonavir.
Darunavir Cmin with Rosuvastatin
|
2744 ng/mL
Interval 2157.0 to 3492.0
|
—
|
—
|
|
To Investigate the Effect of Rosuvastatin on the Steady State Pharmacokinetics of Darunavir/Ritonavir.
Ritonavir Cmin with Rousuvastatin present
|
148 ng/mL
Interval 107.0 to 204.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 45 daysPopulation: Individuals taking medications with measurements of LDL
LDL values
Outcome measures
| Measure |
Rosuvastatin
n=12 Participants
Rosuvastatin 10 mg daily for 7 days.
|
Rosuvastatin-Darunavir-Ritonavir
n=12 Participants
Rosuvastatin 10 mg daily, Darunavir 600 mg and Ritonavir 100 mg twice daily for 7 days
|
Rosuvastatin+Darunavir/Ritonavir
n=12 Participants
LDL values with all three medications
|
|---|---|---|---|
|
To Compare the Change in Low-density Lipoprotein (LDL) Cholesterol With Rosuvastatin Therapy Alone, Darunavir/Ritonavir Therapy Alone and With the Co-administration of Rosuvastatin and Darunavir/Ritonavir.
|
85 mg/dL
Interval 55.0 to 96.0
|
115 mg/dL
Interval 85.0 to 148.0
|
80 mg/dL
Interval 69.0 to 101.0
|
Adverse Events
Darunavir+Ritonavir
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Rosuvastatin
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Darunavir, Ritonavir and Rosuvastatin
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Darunavir+Ritonavir
n=15 participants at risk
Darunavir 600 mg and ritonavir 100 mg twice daily x 7 days
|
Rosuvastatin
n=14 participants at risk
Rosuvastatin 10 mg daily x 7 days
|
Darunavir, Ritonavir and Rosuvastatin
n=12 participants at risk
Darunavir 600 mg and Ritonavir 100 mg twice daily with Rosuvastatin 10 mg daily x 7 days
|
|---|---|---|---|
|
General disorders
Headache
|
6.7%
1/15
|
7.1%
1/14
|
8.3%
1/12
|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15
|
0.00%
0/14
|
8.3%
1/12
|
|
Gastrointestinal disorders
Diarrhea
|
26.7%
4/15
|
0.00%
0/14
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Skin Rash
|
20.0%
3/15
|
0.00%
0/14
|
0.00%
0/12
|
|
Hepatobiliary disorders
Elevated AST
|
13.3%
2/15
|
7.1%
1/14
|
8.3%
1/12
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness
|
0.00%
0/15
|
0.00%
0/14
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/15
|
0.00%
0/14
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
0.00%
0/15
|
7.1%
1/14
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Elevated CPK
|
0.00%
0/15
|
14.3%
2/14
|
0.00%
0/12
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/15
|
7.1%
1/14
|
0.00%
0/12
|
Additional Information
Dr. Carl J. Fichtenbaum
University of Cincinnati College of Medicine
Phone: 513-584-6361
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place