Trial Outcomes & Findings for A Two Way Cross Over Pharmacokinetic Interaction Study Between Raltegravir and Amlodipine in Healthy Volunteers (NCT NCT01841593)
NCT ID: NCT01841593
Last Updated: 2014-09-29
Results Overview
AUC0-24h: Area under the concentration time curve 24 hours in the absence, and presence, of raltegravir
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
19 participants
Primary outcome timeframe
Post-dose on day 7 of daily dosing
Results posted on
2014-09-29
Participant Flow
Participant milestones
| Measure |
Group A (Raltegravir Then Amlodipine)
DAYS 1 to 7: raltegravir 400 mg BID DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: amlodipine 5 mg OD
|
Group B (Amlodipine Then Raltegravir)
DAYS 1 to 7: amlodipine 5 mg OD DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: raltegravir 400 mg BID
|
|---|---|---|
|
First Intervention (Days 1 to 7)
STARTED
|
12
|
7
|
|
First Intervention (Days 1 to 7)
COMPLETED
|
12
|
6
|
|
First Intervention (Days 1 to 7)
NOT COMPLETED
|
0
|
1
|
|
Second Intervention (Days 8 to 14)
STARTED
|
12
|
6
|
|
Second Intervention (Days 8 to 14)
COMPLETED
|
11
|
6
|
|
Second Intervention (Days 8 to 14)
NOT COMPLETED
|
1
|
0
|
|
Third Intervention (Days 15 to 21)
STARTED
|
11
|
6
|
|
Third Intervention (Days 15 to 21)
COMPLETED
|
11
|
6
|
|
Third Intervention (Days 15 to 21)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Group A (Raltegravir Then Amlodipine)
DAYS 1 to 7: raltegravir 400 mg BID DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: amlodipine 5 mg OD
|
Group B (Amlodipine Then Raltegravir)
DAYS 1 to 7: amlodipine 5 mg OD DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: raltegravir 400 mg BID
|
|---|---|---|
|
First Intervention (Days 1 to 7)
Protocol Violation
|
0
|
1
|
|
Second Intervention (Days 8 to 14)
Adverse Event
|
1
|
0
|
Baseline Characteristics
A Two Way Cross Over Pharmacokinetic Interaction Study Between Raltegravir and Amlodipine in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Group A
n=11 Participants
DAYS 1 to 7: raltegravir 400 mg BID DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: amlodipine 5 mg OD
|
Group B
n=6 Participants
DAYS 1 to 7: amlodipine 5 mg OD DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: raltegravir 400 mg BID
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 7 of each intervention (0 (pre-dose), 2, 4, 8 and 12 hours post dose (both drugs) and 24 hours post dose (amlodipine only))Population: Data from all enrolled participants who participated in at least two of the three PK assessments were included in the analysis.
To investigate the pharmacokinetics of raltegravir and amlodipine co-administration. The pharmacokinetic parameters calculated for raltegravir and amlodipine will be trough concentration (Ctrough), defined as the concentration at 24 hours after the observed drug dose, the maximum observed plasma concentration (Cmax), elimination half-life (t1/2), time point at Cmax (Tmax), and total drug exposure, expressed as the area under the plasma concentration-time curve from 0-24 hours after dosing (AUC0-24h). All pharmacokinetic parameters will be calculated using non-compartmental modeling techniques (WinNonlin®) and all statistical calculations performed and analyzed using SAS version 9.1 or SPSS V17.0.
Outcome measures
| Measure |
Raltegravir PK (Alone)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Raltegravir PK (Administered With Amlodipine)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Amlodipine PK (Alone)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Amlodipine PK (Administered With Raltegravir)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
|---|---|---|---|---|
|
Maximum Observed Concentration (Cmax) of Raltegravir and Amlodipine Without and With Co-administration of the Other Studied Drug.
|
1178 ng/mL
Interval 966.0 to 2318.0
|
1866 ng/mL
Interval 1779.0 to 4511.0
|
8.47 ng/mL
Interval 7.58 to 10.0
|
8.49 ng/mL
Interval 7.65 to 9.94
|
PRIMARY outcome
Timeframe: 12 hours post-dose on day 7 of daily dosing.measured concentration 12 hours after dose in the absence, and presence, of amlodipine.
Outcome measures
| Measure |
Raltegravir PK (Alone)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Raltegravir PK (Administered With Amlodipine)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Amlodipine PK (Alone)
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Amlodipine PK (Administered With Raltegravir)
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
|---|---|---|---|---|
|
Raltegravir C12h
|
48 ng/mL
Interval 35.0 to 95.0
|
37 ng/mL
Interval 30.0 to 67.0
|
—
|
—
|
PRIMARY outcome
Timeframe: 12 hours post-dose on day 7 of daily dosing.measured concentration 24 hours after dose in the absence, and presence, of raltegravir
Outcome measures
| Measure |
Raltegravir PK (Alone)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Raltegravir PK (Administered With Amlodipine)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Amlodipine PK (Alone)
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Amlodipine PK (Administered With Raltegravir)
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
|---|---|---|---|---|
|
Amlodipine C24h
|
4.91 ng/mL
Interval 4.23 to 6.36
|
4.55 ng/mL
Interval 4.11 to 5.34
|
—
|
—
|
PRIMARY outcome
Timeframe: Post dose after day 7 of daily dosingAUC0-12h: Area under the concentration time curve over 12 hours in the absence, and presence, of amlodipine.
Outcome measures
| Measure |
Raltegravir PK (Alone)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Raltegravir PK (Administered With Amlodipine)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Amlodipine PK (Alone)
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Amlodipine PK (Administered With Raltegravir)
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
|---|---|---|---|---|
|
Raltegravir AUC(0-12h )
|
4600 ng*h/mL
Interval 3888.0 to 7652.0
|
6410 ng*h/mL
Interval 5649.0 to 12138.0
|
—
|
—
|
PRIMARY outcome
Timeframe: Post-dose on day 7 of daily dosingAUC0-24h: Area under the concentration time curve 24 hours in the absence, and presence, of raltegravir
Outcome measures
| Measure |
Raltegravir PK (Alone)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Raltegravir PK (Administered With Amlodipine)
n=17 Participants
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Amlodipine PK (Alone)
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
Amlodipine PK (Administered With Raltegravir)
Combined analysis - groups A \& B. No period effect due to order of study treatment periods found.
|
|---|---|---|---|---|
|
Amlodipine AUC(0-24h)
|
166.0 ng*h/mL
Interval 146.3 to 202.9
|
165.9 ng*h/mL
Interval 148.7 to 195.8
|
—
|
—
|
Adverse Events
Group A
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Group B
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group A
n=12 participants at risk
DAYS 1 to 7: raltegravir 400 mg BID DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: amlodipine 5 mg OD
|
Group B
n=7 participants at risk
DAYS 1 to 7: amlodipine 5 mg OD DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: raltegravir 400 mg BID
|
|---|---|---|
|
Gastrointestinal disorders
Gastroenteritis
|
8.3%
1/12 • Number of events 1 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
0.00%
0/7 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
Other adverse events
| Measure |
Group A
n=12 participants at risk
DAYS 1 to 7: raltegravir 400 mg BID DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: amlodipine 5 mg OD
|
Group B
n=7 participants at risk
DAYS 1 to 7: amlodipine 5 mg OD DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: raltegravir 400 mg BID
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Cellulitis
|
8.3%
1/12 • Number of events 1 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
0.00%
0/7 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
|
Vascular disorders
thrombophlebitis
|
8.3%
1/12 • Number of events 1 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
0.00%
0/7 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
|
Skin and subcutaneous tissue disorders
gingivitis
|
8.3%
1/12 • Number of events 1 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
0.00%
0/7 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
|
Skin and subcutaneous tissue disorders
pruritic rash
|
8.3%
1/12 • Number of events 1 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
0.00%
0/7 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • Number of events 1 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
0.00%
0/7 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
|
Skin and subcutaneous tissue disorders
pedal oedema
|
8.3%
1/12 • Number of events 1 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
0.00%
0/7 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/12 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
14.3%
1/7 • Number of events 1 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
|
Skin and subcutaneous tissue disorders
insect bite
|
0.00%
0/12 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
14.3%
1/7 • Number of events 1 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
|
Nervous system disorders
light-headed
|
0.00%
0/12 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
14.3%
1/7 • Number of events 1 • Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).
|
Additional Information
Dr. Marta Boffito
SSAT Research, Chelsea & Westminster Hospital
Phone: +442033155601
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place