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The Effect of Antacids on the Pharmacokinetics (PK) of Raltegravir in Human Immunodeficiency Virus (HIV)-Infected Participants (MK-0518-824)

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ClinicalTrials.gov Identifier: NCT02473367
Recruitment Status : Completed
First Posted : June 16, 2015
Results First Posted : September 1, 2016
Last Update Posted : August 27, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infection
Interventions Drug: Raltegravir 1200 mg
Drug: TUMS
Drug: Leader Antacid
Enrollment 20
Recruitment Details Males or females, at least 18 years of age, with HIV infection were enrolled in this trial.
Pre-assignment Details Starting five days prior to Period 1 participants were treated with 1200 mg raltegravir (MK-0518), once daily for five days.
Arm/Group Title Four Period Fixed Sequence
Hide Arm/Group Description All participants entered the first of four treatment periods. Period 1: 1200 mg raltegravir alone; followed by Period 2: 1200 mg raltegravir and TUMS Ultra Strength (US) 1000 taken orally concomitantly; followed by Period 3: 1200 mg raltegravir and 12 hours later with 20 mL Leader Antacid Maximum Strength (MS) taken orally; followed by Period 4: 1200 mg raltegravir and 12 hours later with three tablets of TUMS US 1000 taken orally. There was a maximum 7-day wait between each period where participants were treated once daily with 1200 mg raltegravir.
Period Title: Period 1
Started 20
Completed 20
Not Completed 0
Period Title: Wait 1
Started 20
Completed 19
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Period Title: Period 2
Started 19
Completed 19
Not Completed 0
Period Title: Wait 2
Started 19
Completed 19
Not Completed 0
Period Title: Period 3
Started 19
Completed 19
Not Completed 0
Period Title: Wait 3
Started 19
Completed 19
Not Completed 0
Period Title: Period 4
Started 19
Completed 18
Not Completed 1
Reason Not Completed
Lost to Follow-up             1
Arm/Group Title All Enrolled Participants
Hide Arm/Group Description All participants who enrolled in the study
Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants
49.8  (9.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
2
  10.0%
Male
18
  90.0%
1.Primary Outcome
Title Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hrs (AUC 0-24hr) of Raltegravir Following Once Daily Administration of Raltegravir
Hide Description In Period 1 participants were treated with 1200 mg raltegravir alone; followed by Period 2 where participants were treated with 1200 mg raltegravir and three tablets of TUMS Ultra Strength (US) 1000 taken orally concomitantly; followed by Period 3 where participants were treated with 1200 mg raltegravir and 12 hours later with 20 mL Leader Antacid Maximum Strength (MS) taken orally; followed by Period 4 where participants were treated with 1200 mg raltegravir and 12 hours later with three tablets of TUMS US 1000 taken orally. The wait between Periods was a maximum of 7 days, during which participants were treated with 1200 mg raltegravir once daily. To determine the plasma concentration of raltegravir, blood samples were collected from pre-dose up to 24 hours post-dose, and analysis of variance (ANOVA) modeling was performed on natural log-transformed values to derive geometric least-squares means.
Time Frame Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol: Participants who complied with the protocol sufficiently to ensure that generated data would reflect the effects of treatment, according to the underlying scientific model.
Arm/Group Title Period 1: Raltegravir Only Period 2: Raltegravir + TUMS Concomitantly Period 3: Raltegravir + 12 Hrs Leader Antacid Period 4: Raltegravir + 12 Hrs TUMS
Hide Arm/Group Description:
1200 mg raltegravir, once at the start of Period 1
1200 mg raltegravir and three tablets of TUMS US 1000 concomitantly once at the start of Period 2
1200 mg raltegravir once at the start of Period 3, and 12 hours later with 20 mL Leader Antacid MS
1200 mg raltegravir once at the start of Period 4, and 12 hours later with 3 tablets of TUMS US 1000
Overall Number of Participants Analyzed 20 19 19 19
Least Squares Mean (95% Confidence Interval)
Unit of Measure: hr*µM
53.7
(44.2 to 65.2)
14.8
(12.4 to 17.7)
46.3
(36.0 to 59.6)
48.5
(39.0 to 60.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Period 1: Raltegravir Only, Period 2: Raltegravir + TUMS Concomitantly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geom. least-squares mean ratio (GLSMR)
Estimated Value 0.28
Confidence Interval (2-Sided) 90%
0.24 to 0.32
Estimation Comments Raltegravir+TUMS/Raltegravir only
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Period 1: Raltegravir Only, Period 3: Raltegravir + 12 Hrs Leader Antacid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GLSMR
Estimated Value 0.86
Confidence Interval (2-Sided) 90%
0.73 to 1.03
Estimation Comments Raltegravir+12 Hrs Leader Antacid/Raltegravir only
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Period 1: Raltegravir Only, Period 4: Raltegravir + 12 Hrs TUMS
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GLSMR
Estimated Value 0.90
Confidence Interval (2-Sided) 90%
0.80 to 1.03
Estimation Comments Raltegravir+12 Hrs TUMS/Raltegravir only
2.Primary Outcome
Title Maximum Plasma Concentration (Cmax) of Raltegravir Following Once Daily Administration of Raltegravir
Hide Description In Period 1 participants were treated with 1200 mg raltegravir alone; followed by Period 2 where participants were treated with 1200 mg raltegravir and three tablets of TUMS US 1000 taken orally concomitantly; followed by Period 3 where participants were treated with 1200 mg raltegravir and 12 hours later with 20 mL Leader Antacid MS taken orally; followed by Period 4 where participants were treated with 1200 mg raltegravir and 12 hours later with three tablets of TUMS US 1000 taken orally. The wait between Periods was a maximum of 7 days, during which participants were treated with 1200 mg raltegravir once daily. To determine the plasma concentration of raltegravir, blood samples were collected from pre-dose up to 24 hours post-dose, and ANOVA modeling was performed on natural log-transformed values to derive geometric least-squares means.
Time Frame Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol: Participants who complied with the protocol sufficiently to ensure that generated data would reflect the effects of treatment, according to the underlying scientific model.
Arm/Group Title Period 1: Raltegravir Only Period 2: Raltegravir + TUMS Concomitantly Period 3: Raltegravir + 12 Hrs Leader Antacid Period 4: Raltegravir + 12 Hrs TUMS
Hide Arm/Group Description:
1200 mg raltegravir, once at the start of Period 1
1200 mg raltegravir and three tablets of TUMS US 1000 concomitantly once at the start of Period 2
1200 mg raltegravir once at the start of Period 3, and 12 hours later with 20 mL Leader Antacid MS
1200 mg raltegravir once at the start of Period 4, and 12 hours later with 3 tablets of TUMS US 1000
Overall Number of Participants Analyzed 20 19 19 19
Least Squares Mean (95% Confidence Interval)
Unit of Measure: nM
20000
(16500 to 24300)
5240
(4230 to 6490)
17300
(12800 to 23300)
19500
(15900 to 24000)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Period 1: Raltegravir Only, Period 2: Raltegravir + TUMS Concomitantly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GLSMR
Estimated Value 0.26
Confidence Interval (2-Sided) 90%
0.21 to 0.32
Estimation Comments Raltegravir+TUMS/Raltegravir only
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Period 1: Raltegravir Only, Period 3: Raltegravir + 12 Hrs Leader Antacid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GLSMR
Estimated Value 0.86
Confidence Interval (2-Sided) 90%
0.65 to 1.15
Estimation Comments Raltegravir+12 Hrs Leader Antacid/Raltegravir only
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Period 1: Raltegravir Only, Period 4: Raltegravir + 12 Hrs TUMS
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GLSMR
Estimated Value 0.98
Confidence Interval (2-Sided) 90%
0.81 to 1.17
Estimation Comments Raltegravir+12 Hrs TUMS/Raltegravir only
3.Primary Outcome
Title Plasma Concentration at 24 Hrs Post-dose (C24hr) of Raltegravir Following Once Daily Administration of Raltegravir
Hide Description In Period 1 participants were treated with 1200 mg raltegravir alone; followed by Period 2 where participants were treated with 1200 mg raltegravir and three tablets of TUMS US 1000 taken orally concomitantly; followed by Period 3 where participants were treated with 1200 mg raltegravir and 12 hours later with 20 mL Leader Antacid MS taken orally; followed by Period 4 where participants were treated with 1200 mg raltegravir and 12 hours later with three tablets of TUMS US 1000 taken orally. The wait between Periods was a maximum of 7 days, during which participants were treated with 1200 mg raltegravir once daily. To determine the plasma concentration of raltegravir, blood samples were collected at 24 hours post-dose, and ANOVA modeling was performed on natural log-transformed values to derive geometric least-squares means.
Time Frame 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol: Participants who complied with the protocol sufficiently to ensure that generated data would reflect the effects of treatment, according to the underlying scientific model.
Arm/Group Title Period 1: Raltegravir Only Period 2: Raltegravir + TUMS Concomitantly Period 3: Raltegravir + 12 Hrs Leader Antacid Period 4: Raltegravir + 12 Hrs TUMS
Hide Arm/Group Description:
1200 mg raltegravir, once at the start of Period 1
1200 mg raltegravir and three tablets of TUMS US 1000 concomitantly once at the start of Period 2
1200 mg raltegravir once at the start of Period 3, and 12 hours later with 20 mL Leader Antacid MS
1200 mg raltegravir once at the start of Period 4, and 12 hours later with 3 tablets of TUMS US 1000
Overall Number of Participants Analyzed 20 19 19 19
Least Squares Mean (95% Confidence Interval)
Unit of Measure: nM
75.6
(55.3 to 103)
39.6
(29.9 to 52.5)
32.0
(23.7 to 43.2)
32.4
(24.6 to 42.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Period 1: Raltegravir Only, Period 2: Raltegravir + TUMS Concomitantly
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GLSMR
Estimated Value 0.52
Confidence Interval (2-Sided) 90%
0.45 to 0.61
Estimation Comments Raltegravir+TUMS/Raltegravir only
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Period 1: Raltegravir Only, Period 3: Raltegravir + 12 Hrs Leader Antacid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GLSMR
Estimated Value 0.42
Confidence Interval (2-Sided) 90%
0.34 to 0.52
Estimation Comments Raltegravir+12 Hrs Leader Antacid/Raltegravir only
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Period 1: Raltegravir Only, Period 4: Raltegravir + 12 Hrs TUMS
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GLSMR
Estimated Value 0.43
Confidence Interval (2-Sided) 90%
0.36 to 0.51
Estimation Comments Raltegravir+12 Hrs TUMS/Raltegravir only
Time Frame Periods 1-3: up to 24 hours after treatment with raltegravir; Period 4: up to 14 days after treatment with raltegravir
Adverse Event Reporting Description Participants who received at least one dose of raltegravir
 
Arm/Group Title Period 1: Raltegravir Only Period 2: Raltegravir + TUMS Concomitantly Period 3: Raltegravir + 12 Hrs Leader Antacid Period 4: Raltegravir + 12 Hrs TUMS
Hide Arm/Group Description 1200 mg raltegravir, once at the start of Period 1 1200 mg raltegravir and three tablets of TUMS US 1000 concomitantly once at the start of Period 2 1200 mg raltegravir once at the start of Period 3, and 12 hours later with 20 mL Leader Antacid MS 1200 mg raltegravir once at the start of Period 4, and 12 hours later with 3 tablets of TUMS US 1000
All-Cause Mortality
Period 1: Raltegravir Only Period 2: Raltegravir + TUMS Concomitantly Period 3: Raltegravir + 12 Hrs Leader Antacid Period 4: Raltegravir + 12 Hrs TUMS
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Period 1: Raltegravir Only Period 2: Raltegravir + TUMS Concomitantly Period 3: Raltegravir + 12 Hrs Leader Antacid Period 4: Raltegravir + 12 Hrs TUMS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/20 (0.00%)      1/19 (5.26%)      0/19 (0.00%)      1/19 (5.26%)    
General disorders         
Chest pain  1  0/20 (0.00%)  0 0/19 (0.00%)  0 0/19 (0.00%)  0 1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  0/20 (0.00%)  0 0/19 (0.00%)  0 0/19 (0.00%)  0 1/19 (5.26%)  1
Skin and subcutaneous tissue disorders         
Rash  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/19 (0.00%)  0 0/19 (0.00%)  0
Vascular disorders         
Orthostatic hypotension  1  0/20 (0.00%)  0 0/19 (0.00%)  0 0/19 (0.00%)  0 1/19 (5.26%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Period 1: Raltegravir Only Period 2: Raltegravir + TUMS Concomitantly Period 3: Raltegravir + 12 Hrs Leader Antacid Period 4: Raltegravir + 12 Hrs TUMS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/20 (45.00%)      4/19 (21.05%)      5/19 (26.32%)      5/19 (26.32%)    
Blood and lymphatic system disorders         
Thrombocytopenia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/19 (0.00%)  0 0/19 (0.00%)  0
Gastrointestinal disorders         
Constipation  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/19 (0.00%)  0 0/19 (0.00%)  0
Diarrhoea  1  1/20 (5.00%)  1 1/19 (5.26%)  1 2/19 (10.53%)  2 0/19 (0.00%)  0
Dyspepsia  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/19 (5.26%)  1 0/19 (0.00%)  0
Vomiting  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/19 (5.26%)  1 0/19 (0.00%)  0
General disorders         
Non-cardiac chest pain  1  0/20 (0.00%)  0 0/19 (0.00%)  0 0/19 (0.00%)  0 1/19 (5.26%)  1
Infections and infestations         
Upper respiratory tract infection  1  3/20 (15.00%)  3 2/19 (10.53%)  2 1/19 (5.26%)  1 2/19 (10.53%)  2
Urinary tract infection  1  0/20 (0.00%)  0 0/19 (0.00%)  0 0/19 (0.00%)  0 1/19 (5.26%)  1
Investigations         
Hepatic enzyme increased  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/19 (0.00%)  0 0/19 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Back pain  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/19 (0.00%)  0 0/19 (0.00%)  0
Rhabdomyolysis  1  0/20 (0.00%)  0 0/19 (0.00%)  0 0/19 (0.00%)  0 1/19 (5.26%)  1
Nervous system disorders         
Headache  1  3/20 (15.00%)  3 1/19 (5.26%)  1 0/19 (0.00%)  0 0/19 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Cough  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/19 (0.00%)  0 0/19 (0.00%)  0
Skin and subcutaneous tissue disorders         
Dermatitis contact  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/19 (5.26%)  1 0/19 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 18.1
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 trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
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
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02473367     History of Changes
Other Study ID Numbers: 0518-824
First Submitted: June 12, 2015
First Posted: June 16, 2015
Results First Submitted: July 19, 2016
Results First Posted: September 1, 2016
Last Update Posted: August 27, 2018