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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01622673
First received: June 15, 2012
Last updated: July 16, 2014
Last verified: July 2014
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
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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.

Pre-Assignment 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 2-day 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 2-day 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 2-day 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 2-day 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 2-day 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 2-day 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
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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 2-day 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 2-day 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 2-day 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 2-day 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 2-day 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 2-day 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
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1.  Primary:   Least Squares Mean Steady State Plasma Concentration (C12hrs) of Raltegravir After Coadministration of Antacid (Primary Hypothesis)   [ Time Frame: 12 hours postdose ]
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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
Non-Inferiority/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 non-inferiority 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
Non-Inferiority/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 non-inferiority 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 ]

3.  Primary:   Least Squares Mean Steady State Area Under the Plasma Concentration-time Curve (AUC0-12hrs) 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 ]

4.  Primary:   Least Squares Mean Steady State Area Under the Plasma Concentration-Time (AUC0-12hrs) 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 ]

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 ]

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 ]

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 ]

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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp.
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com


Publications of Results:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01622673     History of Changes
Other Study ID Numbers: 0518-247
Study First Received: June 15, 2012
Results First Received: July 11, 2013
Last Updated: July 16, 2014
Health Authority: United States: Food and Drug Administration