Trial Outcomes & Findings for Pharmacokinetics of Lopinavir/Ritonavir at Three Different Doses. (NCT NCT00985543)

Results Overview

Pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval following administration of lopinavir/ritonavir 400/100mg, 200/150mg and 200/50mg twice daily.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

22 participants

Primary outcome timeframe

at the end of each 7-day dosing phase

Results posted on

2011-03-29

Participant Flow

Participant milestones

Participant milestones
Measure	All Study Participants All participants were given three sequential doses of lopinavir/ritonavir: lopinavir/ritonavir 400/100mg twice daily (2 heat-stable 200/50mg tablets BID), lopinavir/ritonavir 200/150mg twice daily (1 heat-stable 200/50mg tablet BID plus 1 ritonavir 100mg capsule BID), lopinavir/ritonavir 200/50mg twice daily (1 heat-stable 200/50mg tablet BID). Each dosing phase lasted for 7 days and each phase was separated by a 7-day wash-out period. Pharmacokinetic evaluations were made over a 12-hour interval at the end of each dosing phase.
Overall Study STARTED	22
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of Lopinavir/Ritonavir at Three Different Doses.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=22 Participants All participants were given three sequential doses of lopinavir/ritonavir: lopinavir/ritonavir 400/100mg twice daily (2 heat-stable 200/50mg tablets BID), lopinavir/ritonavir 200/150mg twice daily (1 heat-stable 200/50mg tablet BID plus 1 ritonavir 100mg capsule BID), lopinavir/ritonavir 200/50mg twice daily (1 heat-stable 200/50mg tablet BID). Each dosing phase lasted for 7 days and each phase was separated by a 7-day wash-out period. Pharmacokinetic evaluations were made over a 12-hour interval at the end of each dosing phase.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	36 years STANDARD_DEVIATION 9.49 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Region of Enrollment United Kingdom	22 participants n=5 Participants

PRIMARY outcome

Timeframe: at the end of each 7-day dosing phase

Population: 22 participants completed the three sequential dosing phases and pharmacokinetic evaluations as per protocol. The same 22 participants are in the analysis population for each lopinavir/ritonavir dose (arm).

Pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval following administration of lopinavir/ritonavir 400/100mg, 200/150mg and 200/50mg twice daily.

Outcome measures

Outcome measures
Measure	LPV/r 400/100 mg n=22 Participants Lopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID))	LPV/r 200/150 mg n=22 Participants Lopinavir/ritonavir 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID)	LPV/r 200/50 mg n=22 Participants Lopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID)
Plasma Lopinavir/Ritonavir Concentrations as Measured by the Area Under the Curve (AUC 0-12h).	99599 ng.h/mL Interval 87180.0 to 113787.0	73603 ng.h/mL Interval 65121.0 to 83191.0	45146 ng.h/mL Interval 39251.0 to 51927.0

SECONDARY outcome

Timeframe: Up to 11 weeks from screening to final study visit

Population: 22 participants completed the three sequential dosing phases and pharmacokinetic evaluations as per protocol. The same 22 participants are in the analysis population for each lopinavir/ritonavir dose (arm).

Number of reported adverse events, severity of adverse events and relationship to study drug was assessed by questions, physical examination and laboratory parameters. Adverse event data was used to assess the safety and tolerability of low lopinavir/ritonavir doses.

Outcome measures

Outcome measures
Measure	LPV/r 400/100 mg n=22 Participants Lopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID))	LPV/r 200/150 mg n=22 Participants Lopinavir/ritonavir 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID)	LPV/r 200/50 mg n=22 Participants Lopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID)
Adverse Events	27 number of adverse events	2 number of adverse events	4 number of adverse events

Adverse Events

All Study Participants

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	All Study Participants n=22 participants at risk All participants were given three sequential doses of lopinavir/ritonavir: lopinavir/ritonavir 400/100mg twice daily (2 heat-stable 200/50mg tablets BID), lopinavir/ritonavir 200/150mg twice daily (1 heat-stable 200/50mg tablet BID plus 1 ritonavir 100mg capsule BID), lopinavir/ritonavir 200/50mg twice daily (1 heat-stable 200/50mg tablet BID). Each dosing phase lasted for 7 days and each phase was separated by a 7-day wash-out period.
Gastrointestinal disorders Diarrhoea	31.8% 7/22 • Number of events 7 • Up to 11 weeks from screening visit until the participant's final study visit. Any adverse event that occurred after the reporting period that the PI assesses as possibly, probably or definitely related to the study drug was also reported.
General disorders Fatigue	18.2% 4/22 • Number of events 4 • Up to 11 weeks from screening visit until the participant's final study visit. Any adverse event that occurred after the reporting period that the PI assesses as possibly, probably or definitely related to the study drug was also reported.
General disorders Headache	18.2% 4/22 • Number of events 4 • Up to 11 weeks from screening visit until the participant's final study visit. Any adverse event that occurred after the reporting period that the PI assesses as possibly, probably or definitely related to the study drug was also reported.

Additional Information

Dr Marta Boffito

St Stephens Centre, Chelsea and Westminster Hospital

Phone: +44 2088 466 507

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI shall not publish or otherwise disseminate the conclusions of the Study, including all or any part of the Results without the prior written consent of the Sponsor, such consent not to be unreasonably withheld or delayed. Any publication or other dissemination of the conclusions of the Study by the PI shall not occur until the Sponsor has published the conclusions of the Study.
Publication restrictions are in place

Restriction type: OTHER