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A Pharmacokinetic Study to Evaluate the Effect of Antacids on Raltegravir (MK-0518) in HIV-Infected Participants (MK-0518-247)

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ClinicalTrials.gov Identifier: NCT01622673
Recruitment Status : Completed
First Posted : June 19, 2012
Results First Posted : September 17, 2013
Last Update Posted : March 21, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: Raltegravir
Drug: TUMS® Ultra Strength
Drug: MINTOX® Maximum Strength
Enrollment 27
Recruitment Details  
Pre-assignment Details  
Arm/Group Title RAL, TUMS+RAL, MINTOX+RAL, MINTOX Before RAL, MINTOX After RAL TUMS+RAL, MINTOX+RAL, RAL, MINTOX Before RAL, MINTOX After RAL MINTOX+RAL, RAL, TUMS+RAL, MINTOX Before RAL, MINTOX After RAL RAL, MINTOX+RAL, TUMS+RAL, MINTOX After RAL, MINTOX Before RAL TUMS+RAL, RAL, MINTOX+RAL, MINTOX After RAL, MINTOX Before RAL MINTOX+RAL, TUMS+RAL, RAL, MINTOX After RAL, MINTOX Before RAL
Hide Arm/Group Description Participants received Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by MINTOX® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a 2-day washout between treatment periods. Participants received TUMS® + Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. Participants received MINTOX® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. Participants received Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. Participants received TUMS® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by MINTOX® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. Participants received MINTOX® + Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods.
Period Title: Treatment Period 1
Started 4 5 4 6 4 4
Completed 4 4 4 5 4 4
Not Completed 0 1 0 1 0 0
Reason Not Completed
Withdrawal by Subject             0             0             0             1             0             0
Protocol Violation             0             1             0             0             0             0
Period Title: Treatment Period 2
Started 4 4 4 5 4 4
Completed 4 4 4 4 4 4
Not Completed 0 0 0 1 0 0
Reason Not Completed
Withdrawal by Subject             0             0             0             1             0             0
Period Title: Treatment Period 3
Started 4 4 4 4 4 4
Completed 4 3 4 4 4 4
Not Completed 0 1 0 0 0 0
Reason Not Completed
Protocol Violation             0             1             0             0             0             0
Period Title: Treatment Period 4
Started 4 3 4 4 4 4
Completed 4 3 4 4 4 4
Not Completed 0 0 0 0 0 0
Period Title: Treatment Period 5
Started 4 3 4 4 4 4
Completed 4 3 4 4 4 4
Not Completed 0 0 0 0 0 0
Arm/Group Title RAL, TUMS+RAL, MINTOX+RAL, MINTOX Before RAL, MINTOX After RAL TUMS+RAL, MINTOX+RAL, RAL, MINTOX Before RAL, MINTOX After RAL MINTOX+RAL, RAL, TUMS+RAL, MINTOX Before RAL, MINTOX After RAL RAL, MINTOX+RAL, TUMS+RAL, MINTOX After RAL, MINTOX Before RAL TUMS+RAL, RAL, MINTOX+RAL, MINTOX After RAL, MINTOX Before RAL MINTOX+RAL, TUMS+RAL, RAL, MINTOX After RAL, MINTOX Before RAL Total
Hide Arm/Group Description Participants received Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by MINTOX® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a 2-day washout between treatment periods. Participants received TUMS® + Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. Participants received MINTOX® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. Participants received MINTOX® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. Participants received Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. Participants received MINTOX® + Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. Total of all reporting groups
Overall Number of Baseline Participants 4 5 4 6 4 4 27
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 5 participants 4 participants 6 participants 4 participants 4 participants 27 participants
42.5  (10.4) 46.6  (9.5) 36.8  (15.4) 40.3  (10.3) 39.8  (11.8) 40.8  (11.6) 41.3  (10.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 5 participants 4 participants 6 participants 4 participants 4 participants 27 participants
Female
2
  50.0%
1
  20.0%
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
5
  18.5%
Male
2
  50.0%
4
  80.0%
4
 100.0%
4
  66.7%
4
 100.0%
4
 100.0%
22
  81.5%
1.Primary Outcome
Title Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
Hide Description Participant blood samples were collected to measure the steady state plasma concentration of raltegravir 12 hours after administration alone or with a single dose of antacid. The primary hypothesis compared C12hrs of raltegravir when administered alone with C12hrs of raltegravir when coadministered with TUMS® or MINTOX®.
Time Frame 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included for whom at least one pharmacokinetic (PK) parameter could be calculated for all treatment periods and who did not have any protocol deviation interfering with pharmacokinetics
Arm/Group Title Raltegravir TUMS® + Raltegravir MINTOX® + Raltegravir
Hide Arm/Group Description:
Raltegravir 400 mg every 12 hours
Raltegravir 400 mg every 12 hours. A single dose of TUMS® 1000 mg (3 tablets) was coadministered with raltegravir on the day of pharmacokinetic (PK) sampling
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was coadministered with raltegravir on the day of PK sampling
Overall Number of Participants Analyzed 26 24 25
Least Squares Mean (95% Confidence Interval)
Unit of Measure: nM
132.30
(101.14 to 173.05)
89.75
(68.08 to 118.32)
49.38
(37.62 to 64.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Raltegravir, TUMS® + Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% confidence interval (CI) falls above 0.4 for the geometric least squares mean ratio for TUMS® + raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and treatment period and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.678
Confidence Interval (2-Sided) 90%
0.531 to 0.866
Estimation Comments The parameter estimated, geometric least squares mean ratio, is geometric least squares mean C12hrs for TUMS® + raltegravir / geometric least squares mean C12hrs for raltegravir alone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Raltegravir, MINTOX® + Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% CI falls above 0.4 for the geometric least squares mean ratio for MINTOX® + raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and treatment period and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.373
Confidence Interval (2-Sided) 90%
0.293 to 0.475
Estimation Comments The parameter estimated, geometric least squares mean ratio, is the geometric least squares mean C12hrs for MINTOX® + raltegravir / geometric least squares mean C12hrs for raltegravir alone
2.Primary Outcome
Title Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
Hide Description Participant blood samples were collected to measure the steady state plasma concentration of raltegravir 12 hours after administration alone or before or after a single dose of antacid. The secondary hypothesis compared C12hrs of raltegravir when administered alone with C12hrs of raltegravir when administered 2 hours before or after MINTOX®.
Time Frame 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included for whom at least one PK parameter could be calculated for all treatment periods and who did not have any protocol deviation interfering with pharmacokinetics
Arm/Group Title Raltegravir MINTOX® Before Raltegravir MINTOX® After Raltegravir
Hide Arm/Group Description:
Raltegravir 400 mg every 12 hours
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours before raltegravir on the day of PK sampling
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours after raltegravir on the day of PK sampling
Overall Number of Participants Analyzed 26 23 23
Least Squares Mean (95% Confidence Interval)
Unit of Measure: nM
125.75
(94.33 to 167.62)
54.92
(41.36 to 72.91)
54.47
(40.95 to 72.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Raltegravir, MINTOX® Before Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% confidence interval (CI) falls above 0.4 for the geometric least squares mean ratio for MINTOX® before raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.437
Confidence Interval (2-Sided) 90%
0.344 to 0.554
Estimation Comments The parameter estimated, geometric least squares mean ratio, is geometric least squares mean C12hrs for MINTOX® before raltegravir / geometric least squares mean C12hrs for raltegravir alone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Raltegravir, MINTOX® After Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% confidence interval (CI) falls above 0.4 for the geometric least squares mean ratio for MINTOX® after raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.433
Confidence Interval (2-Sided) 90%
0.341 to 0.550
Estimation Comments The parameter estimated, geometric least squares mean ratio, is geometric least squares mean C12hrs for MINTOX® after raltegravir / geometric least squares mean C12hrs for raltegravir alone
3.Primary Outcome
Title Least Squares Mean Steady State Area Under the Plasma Concentration-time Curve (AUC0-12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
Hide Description Participant blood samples were collected to measure the steady state AUC of raltegravir up to 12 hours after administration alone or with a single dose of antacid. The primary hypothesis compared AUC0-12hrs of raltegravir when administered alone with AUC0-12hrs of raltegravir when coadministered with TUMS® or MINTOX®.
Time Frame Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included for whom at least one PK parameter could be calculated for all treatment periods and who did not have any protocol deviation interfering with pharmacokinetics
Arm/Group Title Raltegravir TUMS® + Raltegravir MINTOX® + Raltegravir
Hide Arm/Group Description:
Raltegravir 400 mg every 12 hours
Raltegravir 400 mg every 12 hours. A single dose of TUMS® 1000 mg (3 tablets) was coadministered with raltegravir on the day of PK sampling
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was coadministered with raltegravir on the day of PK sampling
Overall Number of Participants Analyzed 26 24 25
Least Squares Mean (95% Confidence Interval)
Unit of Measure: nM*hr
16399.76
(12728.79 to 21129.44)
7294.30
(5613.53 to 9478.31)
8358.67
(6456.83 to 10820.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Raltegravir, TUMS® + Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% confidence interval (CI) falls above 0.4 for the geometric least squares mean ratio for TUMS® + raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and treatment period and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.445
Confidence Interval (2-Sided) 90%
0.350 to 0.565
Estimation Comments The parameter estimated, geometric least squares mean ratio, is geometric least squares mean AUC0-12hrs for TUMS® + raltegravir / geometric least squares mean AUC0-12hrs for raltegravir alone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Raltegravir, MINTOX® + Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% confidence interval (CI) falls above 0.4 for the geometric least squares mean ratio for MINTOX® + raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and treatment period and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.510
Confidence Interval (2-Sided) 90%
0.402 to 0.646
Estimation Comments The parameter estimated, geometric least squares mean ratio, is geometric least squares mean AUC0-12hrs for MINTOX® + raltegravir / geometric least squares mean AUC0-12hrs for raltegravir alone
4.Primary Outcome
Title Least Squares Mean Steady State Area Under the Plasma Concentration-Time (AUC0-12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
Hide Description Participant blood samples were collected to measure the steady state AUC of raltegravir up to 12 hours after administration alone or before or after a single dose of antacid. The secondary hypothesis compared AUC0-12hrs of raltegravir when administered alone with AUC0-12hrs of raltegravir when administered 2 hours before or after MINTOX®.
Time Frame Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included for whom at least one PK parameter could be calculated for all treatment periods and who did not have any protocol deviation interfering with pharmacokinetics
Arm/Group Title Raltegravir MINTOX® Before Raltegravir MINTOX® After Raltegravir
Hide Arm/Group Description:
Raltegravir 400 mg every 12 hours
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours before raltegravir on the day of PK sampling
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours after raltegravir on the day of PK sampling
Overall Number of Participants Analyzed 26 23 23
Least Squares Mean (95% Confidence Interval)
Unit of Measure: nM*hr
17577.15
(13353.74 to 23136.29)
8521.95
(5572.42 to 13032.70)
12226.11
(7988.11 to 18712.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Raltegravir, MINTOX® Before Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% confidence interval (CI) falls above 0.4 for the geometric least squares mean ratio for MINTOX® before raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.485
Confidence Interval (2-Sided) 90%
0.351 to 0.669
Estimation Comments The parameter estimated, geometric least squares mean ratio, is geometric least squares mean AUC0-12hrs for MINTOX® before raltegravir / geometric least squares mean AUC0-12hrs for raltegravir alone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Raltegravir, MINTOX® After Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% confidence interval (CI) falls above 0.4 for the geometric least squares mean ratio for MINTOX® after raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.696
Confidence Interval (2-Sided) 90%
0.504 to 0.960
Estimation Comments The parameter estimated, geometric least squares mean ratio, is geometric least squares mean AUC0-12hrs for MINTOX® after raltegravir / geometric least squares mean AUC0-12hrs for raltegravir alone
5.Primary Outcome
Title Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
Hide Description Participant blood samples were collected to measure the steady state maximum plasma concentration of raltegravir when administered alone or with a single dose of antacid. The primary hypothesis compared Cmax of raltegravir when administered alone with Cmax of raltegravir when coadministered with TUMS® or MINTOX®.
Time Frame Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included for whom at least one PK parameter could be calculated for all treatment periods and who did not have any protocol deviation interfering with pharmacokinetics
Arm/Group Title Raltegravir TUMS® + Raltegravir MINTOX® + Raltegravir
Hide Arm/Group Description:
Raltegravir 400 mg every 12 hours
Raltegravir 400 mg every 12 hours. A single dose of TUMS® 1000 mg (3 tablets) was coadministered with raltegravir on the day of PK sampling
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was coadministered with raltegravir on the day of PK sampling
Overall Number of Participants Analyzed 26 24 25
Least Squares Mean (95% Confidence Interval)
Unit of Measure: nM
5427.15
(4132.93 to 7126.66)
2584.78
(1949.15 to 3427.70)
3013.88
(2282.54 to 3979.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Raltegravir, TUMS® + Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% confidence interval (CI) falls above 0.4 for the geometric least squares mean ratio for TUMS® + raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and treatment period and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.476
Confidence Interval (2-Sided) 90%
0.362 to 0.627
Estimation Comments The parameter estimated, geometric least squares mean ratio, is geometric least squares mean Cmax for TUMS® + raltegravir / geometric least squares mean Cmax for raltegravir alone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Raltegravir, MINTOX® + Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% CI falls above 0.4 for the geometric least squares mean ratio for MINTOX® + raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and treatment period and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.555
Confidence Interval (2-Sided) 95%
0.423 to 0.729
Estimation Comments The parameter estimated, geometric least squares mean ratio, is the geometric least squares mean Cmax for MINTOX® + raltegravir / geometric least squares mean Cmax for raltegravir alone
6.Primary Outcome
Title Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
Hide Description Participant blood samples were collected to measure the maximum steady state plasma concentration of raltegravir after administration alone or before or after a single dose of antiacid. The secondary hypothesis compared Cmax of raltegravir when administered alone with Cmax of raltegravir when administered 2 hours before or after MINTOX®.
Time Frame Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included for whom at least one PK parameter could be calculated for all treatment periods and who did not have any protocol deviation interfering with pharmacokinetics
Arm/Group Title Raltegravir MINTOX® Before Raltegravir MINTOX® After Raltegravir
Hide Arm/Group Description:
Raltegravir 400 mg every 12 hours
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours before raltegravir on the day of PK sampling
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours after raltegravir on the day of PK sampling
Overall Number of Participants Analyzed 26 23 23
Least Squares Mean (95% Confidence Interval)
Unit of Measure: nM
5678.90
(4263.73 to 7563.78)
2753.64
(1689.26 to 4488.68)
4399.66
(2698.18 to 7174.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Raltegravir, MINTOX® Before Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% confidence interval (CI) falls above 0.4 for the geometric least squares mean ratio for MINTOX® before raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.485
Confidence Interval (2-Sided) 90%
0.332 to 0.709
Estimation Comments The parameter estimated, geometric least squares mean ratio, is geometric least squares mean Cmax for MINTOX® before raltegravir / geometric least squares mean Cmax for raltegravir alone
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Raltegravir, MINTOX® After Raltegravir
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis will be supported if the lower limit of the 90% confidence interval (CI) falls above 0.4 for the geometric least squares mean ratio for MINTOX® after raltegravir versus raltegravir alone
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis incorporated fixed effect for treatment and random effect for participant
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 0.775
Confidence Interval (2-Sided) 90%
0.530 to 1.132
Estimation Comments The parameter estimated, geometric least squares mean ratio, is geometric least squares mean Cmax for MINTOX® after raltegravir / geometric least squares mean Cmax for raltegravir alone
7.Primary Outcome
Title Mean Time to Maximum Plasma Concentration (Tmax) of Raltegravir
Hide Description Participant blood samples were collected to measure the time to achieve the maximum steady state plasma concentration of raltegravir when administered alone or with a single dose of antacid
Time Frame Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
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Hide Analysis Population Description
All participants were included for whom at least one PK parameter could be calculated for all treatment periods and who did not have any protocol deviation interfering with pharmacokinetics
Arm/Group Title Raltegravir TUMS® + Raltegravir MINTOX® + Raltegravir MINTOX® Before Raltegravir MINTOX® After Raltegravir
Hide Arm/Group Description:
Raltegravir 400 mg every 12 hours
Raltegravir 400 mg every 12 hours. A single dose of TUMS® 1000 mg (3 tablets) was coadministered with raltegravir on the day of PK sampling
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was coadministered with raltegravir on the day of PK sampling
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours before raltegravir on the day of PK sampling
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours after raltegravir on the day of PK sampling
Overall Number of Participants Analyzed 26 24 25 23 23
Mean (Standard Deviation)
Unit of Measure: hr
2.06  (1.23) 2.08  (1.64) 1.48  (0.94) 1.52  (1.17) 1.78  (1.37)
8.Primary Outcome
Title Number of Participants With Any Clinical or Laboratory Adverse Event (AE)
Hide Description

An AE is defined as any unfavorable and unintended change in the

structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience.

Time Frame Up to 7 days after the last dose of study drug
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Hide Analysis Population Description
All subjects who received any amount of the study drug were included in the safety population
Arm/Group Title Raltegravir TUMS® + Raltegravir MINTOX® + Raltegravir MINTOX® Before Raltegravir MINTOX® After Raltegravir
Hide Arm/Group Description:
Raltegravir 400 mg every 12 hours
Raltegravir 400 mg every 12 hours. A single dose of TUMS® 1000 mg (3 tablets) was coadministered with raltegravir on the day of AE assessment
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was coadministered with raltegravir on the day of AE assessment
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours before raltegravir on the day of AE assessment
Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours after raltegravir on the day of AE assessment
Overall Number of Participants Analyzed 26 25 25 23 23
Measure Type: Number
Unit of Measure: participants
1 2 2 2 1
Time Frame Up to 7 days after the last dose of study drug
Adverse Event Reporting Description All subjects who received any amount of the study drug were included in the safety population.
 
Arm/Group Title Raltegravir TUMS® + Raltegravir MINTOX® + Raltegravir MINTOX® Before Raltegravir MINTOX® After Raltegravir
Hide Arm/Group Description Raltegravir 400 mg every 12 hours Raltegravir 400 mg every 12 hours. A single dose of TUMS® 1000 mg (3 tablets) was coadministered with raltegravir on the day of PK sampling Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was coadministered with raltegravir on the day of PK sampling Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours before raltegravir on the day of PK sampling Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was administered 2 hours after raltegravir on the day of PK sampling
All-Cause Mortality
Raltegravir TUMS® + Raltegravir MINTOX® + Raltegravir MINTOX® Before Raltegravir MINTOX® After Raltegravir
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Raltegravir TUMS® + Raltegravir MINTOX® + Raltegravir MINTOX® Before Raltegravir MINTOX® After Raltegravir
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/26 (0.00%)   0/25 (0.00%)   0/25 (0.00%)   0/23 (0.00%)   0/23 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Raltegravir TUMS® + Raltegravir MINTOX® + Raltegravir MINTOX® Before Raltegravir MINTOX® After Raltegravir
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/26 (0.00%)   0/25 (0.00%)   0/25 (0.00%)   0/23 (0.00%)   0/23 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01622673     History of Changes
Other Study ID Numbers: 0518-247
First Submitted: June 15, 2012
First Posted: June 19, 2012
Results First Submitted: July 11, 2013
Results First Posted: September 17, 2013
Last Update Posted: March 21, 2017