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In order to define the safe windows for co-dosing of metal-cation antacids with once daily administered raltegravir, this study will evaluate the effect of both calcium carbonate and magnesium/aluminum hydroxide antacids on the pharmacokinetics of raltegravir, due to dosage of 1200 mg raltegravir in HIV-infected participants already taking 400 mg raltegravir twice daily as part of their HIV treatment regimen.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Raltegravir Pre- and 4 Period Sequence | Experimental | Starting five days prior to Period 1 participants will be treated with 1200 mg raltegravir, once daily for five days. In Period 1 participants will be treated with 1200 raltegravir alone; this is followed by Period 2 where participants will be treated with 1200 mg raltegravir and TUMS concomitantly; this is followed by Period 3 where participants will be treated with 1200 mg raltegravir and 12 hours later with Leader Antacid; followed by Period 4 where participants will be treated with 1200 mg raltegravir and 12 hours later with TUMS. The wait between Periods is 2-7 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Raltegravir 1200 mg | Drug | Two tablets of 600 mg raltegravir administered orally, once daily, over 5 days of Pre-treatment, and once at the start of Periods 1-4. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hrs (AUC 0-24hr) of Raltegravir Following Once Daily Administration of Raltegravir | 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. | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose |
| Maximum Plasma Concentration (Cmax) of Raltegravir Following Once Daily Administration of Raltegravir | 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. | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose |
| Plasma Concentration at 24 Hrs Post-dose (C24hr) of Raltegravir Following Once Daily Administration of Raltegravir | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27671833 | Result | Krishna R, East L, Larson P, Valiathan C, Butterfield K, Teng Y, Hernandez-Illas M. Effect of metal-cation antacids on the pharmacokinetics of 1200 mg raltegravir. J Pharm Pharmacol. 2016 Nov;68(11):1359-1365. doi: 10.1111/jphp.12632. Epub 2016 Sep 27. |
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Starting five days prior to Period 1 participants were treated with 1200 mg raltegravir (MK-0518), once daily for five days.
Males or females, at least 18 years of age, with HIV infection were enrolled in this trial.
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| ID | Title | Description |
|---|---|---|
| FG000 | Four Period Fixed Sequence | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Wait 1 |
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| Period 2 |
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| Wait 2 |
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| Period 3 |
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| Wait 3 |
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| Period 4 |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Enrolled Participants | All participants who enrolled in the study |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hrs (AUC 0-24hr) of Raltegravir Following Once Daily Administration of Raltegravir | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | hr*µM | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose |
Periods 1-3: up to 24 hours after treatment with raltegravir; Period 4: up to 14 days after treatment with raltegravir
Participants who received at least one dose of raltegravir
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Period 1: Raltegravir Only | 1200 mg raltegravir, once at the start of Period 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chest pain | General disorders | MedDRA version 18.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 18.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| D000068898 | Raltegravir Potassium |
| ID | Term |
|---|---|
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| TUMS | Drug | Three tablets of TUMS Ultra Strength (US) 1000, taken orally, concomitantly with raltegravir in Period 2, and 12 hours after raltegravir in Period 4 |
|
| Leader Antacid | Drug | 20 mL Leader Antacid Maximum Strength (MS) taken orally 12 hours after raltegravir, in Period 3 |
|
| 24 hours post-dose |
|
|
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
|
|
| Primary | Maximum Plasma Concentration (Cmax) of Raltegravir Following Once Daily Administration of Raltegravir | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | nM | Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose |
|
|
|
|
| Primary | Plasma Concentration at 24 Hrs Post-dose (C24hr) of Raltegravir Following Once Daily Administration of Raltegravir | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | nM | 24 hours post-dose |
|
|
|
|
| 0 |
| 20 |
| 9 |
| 20 |
| EG001 | Period 2: Raltegravir + TUMS Concomitantly | 1200 mg raltegravir and three tablets of TUMS US 1000 concomitantly once at the start of Period 2 | 1 | 19 | 4 | 19 |
| EG002 | Period 3: Raltegravir + 12 Hrs Leader Antacid | 1200 mg raltegravir once at the start of Period 3, and 12 hours later with 20 mL Leader Antacid MS | 0 | 19 | 5 | 19 |
| EG003 | Period 4: Raltegravir + 12 Hrs TUMS | 1200 mg raltegravir once at the start of Period 4, and 12 hours later with 3 tablets of TUMS US 1000 | 1 | 19 | 5 | 19 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA version 18.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA version 18.1 | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA version 18.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.1 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA version 18.1 | Systematic Assessment |
|
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.
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| GLSMR |
| 0.86 |
| 2-Sided |
| 90 |
| 0.65 |
| 1.15 |
Raltegravir+12 Hrs Leader Antacid/Raltegravir only |
| Superiority or Other |
| GLSMR | 0.98 | 2-Sided | 90 | 0.81 | 1.17 | Raltegravir+12 Hrs TUMS/Raltegravir only | Superiority or Other |
| GLSMR |
| 0.42 |
| 2-Sided |
| 90 |
| 0.34 |
| 0.52 |
Raltegravir+12 Hrs Leader Antacid/Raltegravir only |
| Superiority or Other |
| GLSMR | 0.43 | 2-Sided | 90 | 0.36 | 0.51 | Raltegravir+12 Hrs TUMS/Raltegravir only | Superiority or Other |