A Pharmacokinetic Study to Evaluate the Effect of Antacids on Raltegravir (MK0518) in HIVInfected Participants (MK0518247)
This study has been completed.
Sponsor:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01622673
First received: June 15, 2012
Last updated: February 6, 2015
Last verified: February 2015
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Results First Received: July 11, 2013
Study Type:  Interventional 

Study Design:  Allocation: Randomized; Endpoint Classification: Pharmacokinetics Study; Intervention Model: Crossover Assignment; Masking: Open Label; Primary Purpose: Treatment 
Condition: 
HIV Infections 
Interventions: 
Drug: Raltegravir Drug: TUMS® Ultra Strength Drug: MINTOX® Maximum Strength 
Participant Flow
Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations 

No text entered. 
PreAssignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment 

No text entered. 
Reporting Groups
Description  

RAL, TUMS+RAL, MINTOX+RAL, MINTOX Before RAL, MINTOX After RAL  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 2day washout between treatment periods. 
TUMS+RAL, MINTOX+RAL, RAL, MINTOX Before RAL, MINTOX After RAL  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 2day washout between treatment periods. 
MINTOX+RAL, RAL, TUMS+RAL, MINTOX Before RAL, MINTOX After RAL  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 2day washout between treatment periods. 
RAL, MINTOX+RAL, TUMS+RAL, MINTOX After RAL, MINTOX Before RAL  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 2day washout between treatment periods. 
TUMS+RAL, RAL, MINTOX+RAL, MINTOX After RAL, MINTOX Before RAL  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 2day washout between treatment periods. 
MINTOX+RAL, TUMS+RAL, RAL, MINTOX After RAL, MINTOX Before RAL  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 2day washout between treatment periods. 
Participant Flow for 5 periods
Period 1: Treatment Period 1
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  

STARTED  4  5  4  6  4  4 
COMPLETED  4  4  4  5  4  4 
NOT COMPLETED  0  1  0  1  0  0 
Withdrawal by Subject  0  0  0  1  0  0 
Protocol Violation  0  1  0  0  0  0 
Period 2: Treatment Period 2
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  

STARTED  4  4  4  5  4  4 
COMPLETED  4  4  4  4  4  4 
NOT COMPLETED  0  0  0  1  0  0 
Withdrawal by Subject  0  0  0  1  0  0 
Period 3: Treatment Period 3
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  

STARTED  4  4  4  4  4  4 
COMPLETED  4  3  4  4  4  4 
NOT COMPLETED  0  1  0  0  0  0 
Protocol Violation  0  1  0  0  0  0 
Period 4: Treatment Period 4
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  

STARTED  4  3  4  4  4  4 
COMPLETED  4  3  4  4  4  4 
NOT COMPLETED  0  0  0  0  0  0 
Period 5: Treatment Period 5
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  

STARTED  4  3  4  4  4  4 
COMPLETED  4  3  4  4  4  4 
NOT COMPLETED  0  0  0  0  0  0 
Baseline Characteristics
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

No text entered. 
Reporting Groups
Description  

RAL, TUMS+RAL, MINTOX+RAL, MINTOX Before RAL, MINTOX After RAL  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 2day washout between treatment periods. 
TUMS+RAL, MINTOX+RAL, RAL, MINTOX Before RAL, MINTOX After RAL  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 2day washout between treatment periods. 
MINTOX+RAL, RAL, TUMS+RAL, MINTOX Before RAL, MINTOX After RAL  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 2day washout between treatment periods. 
RAL, MINTOX+RAL, TUMS+RAL, MINTOX After RAL, MINTOX Before RAL  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 2day washout between treatment periods. 
TUMS+RAL, RAL, MINTOX+RAL, MINTOX After RAL, MINTOX Before RAL  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 2day washout between treatment periods. 
MINTOX+RAL, TUMS+RAL, RAL, MINTOX After RAL, MINTOX Before RAL  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 2day washout between treatment periods. 
Total  Total of all reporting groups 
Baseline Measures
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  

Number of Participants
[units: participants] 
4  5  4  6  4  4  27 
Age
[units: years] Mean (Standard Deviation) 
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) 
Gender
[units: participants] 

Female  2  1  0  2  0  0  5 
Male  2  4  4  4  4  4  22 
Outcome Measures
1. Primary:  Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis) [ Time Frame: 12 hours postdose ] 
Measure Type  Primary 

Measure Title  Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis) 
Measure 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 
Safety Issue  No 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

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 
Reporting Groups
Description  

Raltegravir  Raltegravir 400 mg every 12 hours 
TUMS® + Raltegravir  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 
MINTOX® + Raltegravir  Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was coadministered with raltegravir on the day of PK sampling 
Measured Values
Raltegravir  TUMS® + Raltegravir  MINTOX® + Raltegravir  

Number of Participants Analyzed
[units: participants] 
26  24  25 
Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
[units: nM] Least Squares Mean (95% Confidence Interval) 
132.30
(101.14 to 173.05) 
89.75
(68.08 to 118.32) 
49.38
(37.62 to 64.81) 
Statistical Analysis 1 for Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
Groups ^{[1]}  Raltegravir vs. TUMS® + Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.678 
90% Confidence Interval  0.531 to 0.866 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and treatment period and random effect for participant  
[4]  Other relevant estimation information: 
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 
Statistical Analysis 2 for Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
Groups ^{[1]}  Raltegravir vs. MINTOX® + Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.373 
90% Confidence Interval  0.293 to 0.475 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and treatment period and random effect for participant  
[4]  Other relevant estimation information: 
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:  Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis) [ Time Frame: 12 hours postdose ] 
Measure Type  Primary 

Measure Title  Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis) 
Measure 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 
Safety Issue  No 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

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 
Reporting Groups
Description  

Raltegravir  Raltegravir 400 mg every 12 hours 
MINTOX® Before Raltegravir  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 
MINTOX® After Raltegravir  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 
Measured Values
Raltegravir  MINTOX® Before Raltegravir  MINTOX® After Raltegravir  

Number of Participants Analyzed
[units: participants] 
26  23  23 
Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
[units: nM] Least Squares Mean (95% Confidence Interval) 
125.75
(94.33 to 167.62) 
54.92
(41.36 to 72.91) 
54.47
(40.95 to 72.46) 
Statistical Analysis 1 for Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
Groups ^{[1]}  Raltegravir vs. MINTOX® Before Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.437 
90% Confidence Interval  0.344 to 0.554 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and random effect for participant  
[4]  Other relevant estimation information: 
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 
Statistical Analysis 2 for Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
Groups ^{[1]}  Raltegravir vs. MINTOX® After Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.433 
90% Confidence Interval  0.341 to 0.550 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and random effect for participant  
[4]  Other relevant estimation information: 
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:  Least Squares Mean Steady State Area Under the Plasma Concentrationtime Curve (AUC012hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis) [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose ] 
Measure Type  Primary 

Measure Title  Least Squares Mean Steady State Area Under the Plasma Concentrationtime Curve (AUC012hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis) 
Measure 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 AUC012hrs of raltegravir when administered alone with AUC012hrs 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 
Safety Issue  No 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

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 
Reporting Groups
Description  

Raltegravir  Raltegravir 400 mg every 12 hours 
TUMS® + Raltegravir  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 
MINTOX® + Raltegravir  Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was coadministered with raltegravir on the day of PK sampling 
Measured Values
Raltegravir  TUMS® + Raltegravir  MINTOX® + Raltegravir  

Number of Participants Analyzed
[units: participants] 
26  24  25 
Least Squares Mean Steady State Area Under the Plasma Concentrationtime Curve (AUC012hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
[units: nM*hr] Least Squares Mean (95% Confidence Interval) 
16399.76
(12728.79 to 21129.44) 
7294.30
(5613.53 to 9478.31) 
8358.67
(6456.83 to 10820.68) 
Statistical Analysis 1 for Least Squares Mean Steady State Area Under the Plasma Concentrationtime Curve (AUC012hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
Groups ^{[1]}  Raltegravir vs. TUMS® + Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.445 
90% Confidence Interval  0.350 to 0.565 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and treatment period and random effect for participant  
[4]  Other relevant estimation information: 
The parameter estimated, geometric least squares mean ratio, is geometric least squares mean AUC012hrs for TUMS® + raltegravir / geometric least squares mean AUC012hrs for raltegravir alone 
Statistical Analysis 2 for Least Squares Mean Steady State Area Under the Plasma Concentrationtime Curve (AUC012hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
Groups ^{[1]}  Raltegravir vs. MINTOX® + Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.510 
90% Confidence Interval  0.402 to 0.646 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and treatment period and random effect for participant  
[4]  Other relevant estimation information: 
The parameter estimated, geometric least squares mean ratio, is geometric least squares mean AUC012hrs for MINTOX® + raltegravir / geometric least squares mean AUC012hrs for raltegravir alone 
4. Primary:  Least Squares Mean Steady State Area Under the Plasma ConcentrationTime (AUC012hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis) [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose ] 
Measure Type  Primary 

Measure Title  Least Squares Mean Steady State Area Under the Plasma ConcentrationTime (AUC012hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis) 
Measure 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 AUC012hrs of raltegravir when administered alone with AUC012hrs 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 
Safety Issue  No 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

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 
Reporting Groups
Description  

Raltegravir  Raltegravir 400 mg every 12 hours 
MINTOX® Before Raltegravir  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 
MINTOX® After Raltegravir  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 
Measured Values
Raltegravir  MINTOX® Before Raltegravir  MINTOX® After Raltegravir  

Number of Participants Analyzed
[units: participants] 
26  23  23 
Least Squares Mean Steady State Area Under the Plasma ConcentrationTime (AUC012hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
[units: nM*hr] Least Squares Mean (95% Confidence Interval) 
17577.15
(13353.74 to 23136.29) 
8521.95
(5572.42 to 13032.70) 
12226.11
(7988.11 to 18712.53) 
Statistical Analysis 1 for Least Squares Mean Steady State Area Under the Plasma ConcentrationTime (AUC012hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
Groups ^{[1]}  Raltegravir vs. MINTOX® Before Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.485 
90% Confidence Interval  0.351 to 0.669 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and random effect for participant  
[4]  Other relevant estimation information: 
The parameter estimated, geometric least squares mean ratio, is geometric least squares mean AUC012hrs for MINTOX® before raltegravir / geometric least squares mean AUC012hrs for raltegravir alone 
Statistical Analysis 2 for Least Squares Mean Steady State Area Under the Plasma ConcentrationTime (AUC012hrs) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
Groups ^{[1]}  Raltegravir vs. MINTOX® After Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.696 
90% Confidence Interval  0.504 to 0.960 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and random effect for participant  
[4]  Other relevant estimation information: 
The parameter estimated, geometric least squares mean ratio, is geometric least squares mean AUC012hrs for MINTOX® after raltegravir / geometric least squares mean AUC012hrs for raltegravir alone 
5. Primary:  Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Coadministration of Antacid (Primary Hypothesis) [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose ] 
Measure Type  Primary 

Measure Title  Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Coadministration of Antacid (Primary Hypothesis) 
Measure 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 
Safety Issue  No 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

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 
Reporting Groups
Description  

Raltegravir  Raltegravir 400 mg every 12 hours 
TUMS® + Raltegravir  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 
MINTOX® + Raltegravir  Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was coadministered with raltegravir on the day of PK sampling 
Measured Values
Raltegravir  TUMS® + Raltegravir  MINTOX® + Raltegravir  

Number of Participants Analyzed
[units: participants] 
26  24  25 
Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
[units: nM] Least Squares Mean (95% Confidence Interval) 
5427.15
(4132.93 to 7126.66) 
2584.78
(1949.15 to 3427.70) 
3013.88
(2282.54 to 3979.54) 
Statistical Analysis 1 for Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
Groups ^{[1]}  Raltegravir vs. TUMS® + Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.476 
90% Confidence Interval  0.362 to 0.627 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and treatment period and random effect for participant  
[4]  Other relevant estimation information: 
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 
Statistical Analysis 2 for Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)
Groups ^{[1]}  Raltegravir vs. MINTOX® + Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.555 
95% Confidence Interval  0.423 to 0.729 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and treatment period and random effect for participant  
[4]  Other relevant estimation information: 
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:  Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis) [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose ] 
Measure Type  Primary 

Measure Title  Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis) 
Measure 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 
Safety Issue  No 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

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 
Reporting Groups
Description  

Raltegravir  Raltegravir 400 mg every 12 hours 
MINTOX® Before Raltegravir  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 
MINTOX® After Raltegravir  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 
Measured Values
Raltegravir  MINTOX® Before Raltegravir  MINTOX® After Raltegravir  

Number of Participants Analyzed
[units: participants] 
26  23  23 
Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
[units: nM] Least Squares Mean (95% Confidence Interval) 
5678.90
(4263.73 to 7563.78) 
2753.64
(1689.26 to 4488.68) 
4399.66
(2698.18 to 7174.09) 
Statistical Analysis 1 for Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
Groups ^{[1]}  Raltegravir vs. MINTOX® Before Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.485 
90% Confidence Interval  0.332 to 0.709 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and random effect for participant  
[4]  Other relevant estimation information: 
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 
Statistical Analysis 2 for Least Squares Mean Maximum Plasma Concentration (Cmax) of Raltegravir After Staggered Administration of Antacid (Secondary Hypothesis)
Groups ^{[1]}  Raltegravir vs. MINTOX® After Raltegravir 

NonInferiority/Equivalence Test ^{[2]}  Yes 
Method ^{[3]}  Mixed Models Analysis 
Geometric Least Squares Mean Ratio ^{[4]}  0.775 
90% Confidence Interval  0.530 to 1.132 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

No text entered.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
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  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
Analysis incorporated fixed effect for treatment and random effect for participant  
[4]  Other relevant estimation information: 
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:  Mean Time to Maximum Plasma Concentration (Tmax) of Raltegravir [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose ] 
Measure Type  Primary 

Measure Title  Mean Time to Maximum Plasma Concentration (Tmax) of Raltegravir 
Measure 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 
Safety Issue  No 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

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 
Reporting Groups
Description  

Raltegravir  Raltegravir 400 mg every 12 hours 
TUMS® + Raltegravir  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 
MINTOX® + Raltegravir  Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was coadministered with raltegravir on the day of PK sampling 
MINTOX® Before Raltegravir  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 
MINTOX® After Raltegravir  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 
Measured Values
Raltegravir  TUMS® + Raltegravir  MINTOX® + Raltegravir  MINTOX® Before Raltegravir  MINTOX® After Raltegravir  

Number of Participants Analyzed
[units: participants] 
26  24  25  23  23 
Mean Time to Maximum Plasma Concentration (Tmax) of Raltegravir
[units: hr] Mean (Standard Deviation) 
2.06 (1.23)  2.08 (1.64)  1.48 (0.94)  1.52 (1.17)  1.78 (1.37) 
No statistical analysis provided for Mean Time to Maximum Plasma Concentration (Tmax) of Raltegravir
8. Primary:  Number of Participants With Any Clinical or Laboratory Adverse Event (AE) [ Time Frame: Up to 7 days after the last dose of study drug ] 
Measure Type  Primary 

Measure Title  Number of Participants With Any Clinical or Laboratory Adverse Event (AE) 
Measure 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 
Safety Issue  Yes 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

All subjects who received any amount of the study drug were included in the safety population 
Reporting Groups
Description  

Raltegravir  Raltegravir 400 mg every 12 hours 
TUMS® + Raltegravir  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 
MINTOX® + Raltegravir  Raltegravir 400 mg every 12 hours. A single dose of MINTOX® 20 mL was coadministered with raltegravir on the day of AE assessment 
MINTOX® Before Raltegravir  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 
MINTOX® After Raltegravir  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 
Measured Values
Raltegravir  TUMS® + Raltegravir  MINTOX® + Raltegravir  MINTOX® Before Raltegravir  MINTOX® After Raltegravir  

Number of Participants Analyzed
[units: participants] 
26  25  25  23  23 
Number of Participants With Any Clinical or Laboratory Adverse Event (AE)
[units: participants] 
1  2  2  2  1 
No statistical analysis provided for Number of Participants With Any Clinical or Laboratory Adverse Event (AE)
Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data 

No text entered. 
More Information
Certain Agreements:
Results Point of Contact:
Publications of Results:
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 agreement is:

Results Point of Contact:
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
phone: 18006726372
email: ClinicalTrialsDisclosure@merck.com
Organization: Merck Sharp & Dohme Corp.
phone: 18006726372
email: ClinicalTrialsDisclosure@merck.com
Publications of Results:
Responsible Party:  Merck Sharp & Dohme Corp. 
ClinicalTrials.gov Identifier:  NCT01622673 History of Changes 
Other Study ID Numbers: 
0518247 
Study First Received:  June 15, 2012 
Results First Received:  July 11, 2013 
Last Updated:  February 6, 2015 
Health Authority:  United States: Food and Drug Administration 