Trial Outcomes & Findings for Investigation of Faldaprevir Effect on Pharmacokinetics of Raltegravir (NCT NCT01785160)

Results Overview

AUC tau,ss (area under the concentration-time curve of the Raltegravir in plasma at steady state over the uniform dosing interval tau) Point estimates for the intrasubject ratio of the geometric means (for treatments Test and Reference) of AUC tau,ss and their 2-sided 90% confidence intervals (CI) were calculated. The statistical model was an analysis of variance (ANOVA) on log-transformed parameters including effects for 'subject' and 'treatment'. RAL: Raltegravir , FDV: Faldaprevir

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

25 participants

Primary outcome timeframe

0.5 hours (h) before drug administration and 48 hours (h),60,72,72.5,73,73.5,74,75,76,77,78,80,82 and 84(hours) after administration of RAL alone; 96 h,108,120,120.5,121,121.5,122,123,124, 125,126,128,130 and 132 hours after RAL and FDV administration

Results posted on

2015-08-03

Participant Flow

Participant milestones

Participant milestones
Measure	Overall Study Total number of patients randomised and treated in the study.This was a open label trial with two periods in a fixed sequence. All subjects were to receive the following 2 treatments, A\]Raltegravir B\]Raltegravir+Faldaprevir. The two treatments were separated by washout period of at least 7 days.
Treatment Period 1: Raltegravir STARTED	25
Treatment Period 1: Raltegravir COMPLETED	24
Treatment Period 1: Raltegravir NOT COMPLETED	1
Washout Period of at Least 7 Days STARTED	24
Washout Period of at Least 7 Days COMPLETED	23
Washout Period of at Least 7 Days NOT COMPLETED	1
Treatment Period 2: Raltegravir + Faldap STARTED	23
Treatment Period 2: Raltegravir + Faldap COMPLETED	23
Treatment Period 2: Raltegravir + Faldap NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Overall Study Total number of patients randomised and treated in the study.This was a open label trial with two periods in a fixed sequence. All subjects were to receive the following 2 treatments, A\]Raltegravir B\]Raltegravir+Faldaprevir. The two treatments were separated by washout period of at least 7 days.
Treatment Period 1: Raltegravir Not treated	1
Washout Period of at Least 7 Days Consent withdrawn	1

Baseline Characteristics

Investigation of Faldaprevir Effect on Pharmacokinetics of Raltegravir

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study n=24 Participants Total number of patients randomised and treated in the study.This was a open label trial with two periods in a fixed sequence. All subjects were to receive the following 2 treatments, A\]Raltegravir B\]Raltegravir+Faldaprevir The two treatments were separated by washout period of at least 7 days.
Age, Continuous	40.8 years STANDARD_DEVIATION 8.8 • n=93 Participants
Sex: Female, Male Female	12 Participants n=93 Participants
Sex: Female, Male Male	12 Participants n=93 Participants

PRIMARY outcome

Timeframe: 0.5 hours (h) before drug administration and 48 hours (h),60,72,72.5,73,73.5,74,75,76,77,78,80,82 and 84(hours) after administration of RAL alone; 96 h,108,120,120.5,121,121.5,122,123,124, 125,126,128,130 and 132 hours after RAL and FDV administration

Population: Pharmacokinetic(PK) set:Subjects who received atleast 1 dose of study medication and who provided at least 1 observation for at least 1 PK endpoint without any important protocol violations relevant to the evaluation of relative bioavailability and did not experience emesis at or before 2 times median tmax on the pk study days of both trial periods

AUC tau,ss (area under the concentration-time curve of the Raltegravir in plasma at steady state over the uniform dosing interval tau) Point estimates for the intrasubject ratio of the geometric means (for treatments Test and Reference) of AUC tau,ss and their 2-sided 90% confidence intervals (CI) were calculated. The statistical model was an analysis of variance (ANOVA) on log-transformed parameters including effects for 'subject' and 'treatment'. RAL: Raltegravir , FDV: Faldaprevir

Outcome measures

Outcome measures
Measure	Raltegravir n=24 Participants Raltegravir coated tablets Oral with 240 mL of water Days 1 to 3: 400 mg raltegravir twice daily Day 4: 400 mg raltegravir once daily	Raltegravir + Faldaprevir n=23 Participants Raltegravir coated tablets and Faldaprevir soft gelatin capsules Oral with 240 mL of water Day 1: 400 mg raltegravir twice daily and 240 mg faldaprevir twice daily (loading dose) Days 2 to 5: 400 mg raltegravir twice daily and 240 mg faldaprevir once daily Day 6: 400 mg raltegravir once daily and 240 mg faldaprevir once daily
AUC( Tau,ss)	4070 ng*h/mL Geometric Coefficient of Variation 92.9	11100 ng*h/mL Geometric Coefficient of Variation 78.7

PRIMARY outcome

Timeframe: 0.5 hours (h) before drug administration and 48 hours (h),60,72,72.5,73,73.5,74,75,76,77,78,80,82 and 84(hours) after administration of RAL alone; 96 h,108,120,120.5,121,121.5,122,123,124, 125,126,128,130 and 132hours after RAL and FDV administration

Population: Pharmacokinetic(PK) set:Subjects who received atleast 1 dose of study medication and who provided at least 1 observation for at least 1 PK endpoint without any important protocol violations relevant to the evaluation of relative bioavailability and did not experience emesis at or before 2 times median tmax on the pk study days of both trial periods

C max,ss (maximum measured concentration of the Raltegravir in plasma at steady state) Point estimates for the intrasubject ratio of the geometric means (for treatments Test and Reference) of Cmax,ss and their 2-sided 90% confidence intervals (CI) were calculated. The statistical model was an analysis of variance (ANOVA) on log-transformed parameters including effects for 'subject' and 'treatment'. RAL: Raltegravir , FDV: Faldaprevir

Outcome measures

Outcome measures
Measure	Raltegravir n=24 Participants Raltegravir coated tablets Oral with 240 mL of water Days 1 to 3: 400 mg raltegravir twice daily Day 4: 400 mg raltegravir once daily	Raltegravir + Faldaprevir n=23 Participants Raltegravir coated tablets and Faldaprevir soft gelatin capsules Oral with 240 mL of water Day 1: 400 mg raltegravir twice daily and 240 mg faldaprevir twice daily (loading dose) Days 2 to 5: 400 mg raltegravir twice daily and 240 mg faldaprevir once daily Day 6: 400 mg raltegravir once daily and 240 mg faldaprevir once daily
Cmax ,ss	1300 ng/mL Geometric Coefficient of Variation 115	3220 ng/mL Geometric Coefficient of Variation 108

Adverse Events

Raltegravir

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Raltegravir + Faldaprevir

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Raltegravir n=24 participants at risk coated tablets, oral administration with 240 ml water Raltegravir: low dose oral administration	Raltegravir + Faldaprevir n=23 participants at risk coated tablets and soft gelatine capsule, oral administration with 240 ml water Raltegravir: low dose oral administration Faldaprevir: medium dose oral administration
Nervous system disorders Headache	12.5% 3/24 • Up to 23 days (+1day)	21.7% 5/23 • Up to 23 days (+1day)
Nervous system disorders Dizziness	8.3% 2/24 • Up to 23 days (+1day)	0.00% 0/23 • Up to 23 days (+1day)
Gastrointestinal disorders Nausea	4.2% 1/24 • Up to 23 days (+1day)	26.1% 6/23 • Up to 23 days (+1day)
Gastrointestinal disorders Diarrhoea	4.2% 1/24 • Up to 23 days (+1day)	13.0% 3/23 • Up to 23 days (+1day)
Gastrointestinal disorders Vomiting	0.00% 0/24 • Up to 23 days (+1day)	8.7% 2/23 • Up to 23 days (+1day)
Gastrointestinal disorders Flatulence	8.3% 2/24 • Up to 23 days (+1day)	4.3% 1/23 • Up to 23 days (+1day)
General disorders Fatigue	0.00% 0/24 • Up to 23 days (+1day)	21.7% 5/23 • Up to 23 days (+1day)

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER