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This study evaluated the effect of single doses of a magnesium/aluminum antacid (MAALOX) given 4 and 6 hours before or after administration of raltegravir, on the pharmacokinetics of raltegravir in human immunodeficiency virus (HIV)-infected participants. The study consisted of Part 1 (Periods 1, 2, and 3) and Part 2 (Periods 4 and 5), with each study period separated by a washout period of at least 2 days; Part 1 was separated from Part 2 by a Pause. Each study period had a duration of ≥2 days, and paused for evaluation of Part 1 pharmacokinetics results before continuing to Part 2. The same participants participated in Parts 1 and 2. The primary hypothesis tested (in Part 1) was that raltegravir plasma concentration 12 hours after administration (C 12 hrs) would not differ significantly from raltegravir C 12 hrs when antacid is administered 4 hours before or 4 hours after raltegravir.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ralt→MAL4Ralt→Ralt4MAL→MAL6Ralt→Ralt6MAL | Experimental | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Raltegravir (Ralt) alone in Period 1, MAALOX (MAL) followed 4 hrs later by Ralt in Period 2, Ralt followed 4 hrs later by MAL in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5 |
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| MAL4Ralt→Ralt4MAL→Ralt→MAL6Ralt→Ralt6MAL | Experimental | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: MAL followed 4 hrs later by Ralt in Period 1, Ralt followed 4 hrs later by MAL in Period 2, Ralt alone in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5 |
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| Ralt4MAL→Ralt→MAL4Ralt→MAL6Ralt→Ralt6MAL | Experimental | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt followed 4 hrs later by MAL in Period 1, Ralt alone in Period 2, MAL followed 4 hrs later by Ralt in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Raltegravir (ISENTRESSâ„¢) | Drug | Raltegravir 400 mg oral tablet once every 12 hours. Participants will continue with their other prescribed antiretroviral agents throughout the study. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Concentration of Raltegravir at 12 Hours (C 12 Hrs) in Part 1 | Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration. | 12 hours after dosing on Day 1 of each period |
| Area Under the Plasma Concentration Versus Time Curve (AUC 0-12 Hrs) of Raltegravir in Part 1 | Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir in order to determine the geometric mean area under the curve plasma concentration versus time. | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period |
| Maximum Plasma Concentration (C Max) of Raltegravir in Part 1 | Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean maximum plasma concentration. | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period |
| Plasma Concentration of Raltegravir at 12 Hours (C 12 Hrs) in Part 2 | Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration. | 12 hours after dosing on Day 1 of each period |
| Area Under the Plasma Concentration Versus Time Curve (AUC 0-12 Hrs) of Raltegravir in Part 2 | Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean area under the curve plasma concentration versus time. | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period |
| Maximum Plasma Concentration (C Max) of Raltegravir in Part 2 |
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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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| ID | Type | URL | Comment |
|---|---|---|---|
| CSR Synopsis | View IPD |
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| ID | Title | Description |
|---|---|---|
| FG000 | Ralt-MAL4Ralt-Ralt4MAL-MAL6Ralt-Ralt6MAL | Part 1 was comprised of Periods 1, 2 and 3; Period 3 was followed by a Pause of up to 37 days, before Part 2; Part 2 was comprised of Periods 4 and 5. Each period was separated by a washout of at least 2 days. Each Period had single oral dose treatments as follows: Raltegravir (Ralt) alone in Period 1, MAALOX (MAL) followed 4 hrs later by Ralt in Period 2, Ralt followed 4 hrs later by MAL in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part 1 - Period 1 |
|
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| Ralt→Ralt4MAL→MAL4Ralt→Ralt6MAL→MAL6Ralt | Experimental | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt alone in Period 1, Ralt followed 4 hrs later by MAL in Period 2, MAL followed 4 hrs later by Ralt in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5 |
|
| MAL4Ralt→Ralt→Ralt4MAL→Ralt6MAL→MAL6Ralt | Experimental | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: MAL followed 4 hrs later by Ralt in Period 1, Ralt alone in Period 2, Ralt followed 4 hrs later by MAL in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5 |
|
| Ralt4MAL→MAL4Ralt→Ralt→Ralt6MAL→MAL6Ralt | Experimental | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt followed 4 hrs later by MAL in Period 1, MAL followed 4 hrs later by Ralt in Period 2, Ralt alone in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5 |
|
| MAALOX (MAL) | Drug | MAL (or generic equivalent) 20 mL oral single dose on Day 1 |
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Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean maximum plasma concentration. |
| Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period |
| FG001 | MAL4Ralt-Ralt4MAL-Ralt-MAL6Ralt-Ralt6MAL | Part 1 was comprised of Periods 1, 2 and 3; Period 3 was followed by a Pause of up to 37 days, before Part 2; Part 2 was comprised of Periods 4 and 5. Each period was separated by a washout of at least 2 days. Each Period had single oral dose treatments as follows: MAL followed 4 hrs later by Ralt in Period 1, Ralt followed 4 hrs later by MAL in Period 2, Ralt alone in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5 |
| FG002 | Ralt4MAL-Ralt-MAL4Ralt-MAL6Ralt-Ralt6MAL | Part 1 was comprised of Periods 1, 2 and 3; Period 3 was followed by a Pause of up to 37 days, before Part 2; Part 2 was comprised of Periods 4 and 5. Each period was separated by a washout of at least 2 days. Each Period had single oral dose treatments as follows: Ralt followed 4 hrs later by MAL in Period 1, Ralt alone in Period 2, MAL followed 4 hrs later by Ralt in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5 |
| FG003 | Ralt-Ralt4MAL-MAL4Ralt-Ralt6MAL-MAL6Ralt | Part 1 was comprised of Periods 1, 2 and 3; Period 3 was followed by a Pause of up to 37 days, before Part 2; Part 2 was comprised of Periods 4 and 5. Each period was separated by a washout of at least 2 days. Each Period had single oral dose treatments as follows: Ralt alone in Period 1, Ralt followed 4 hrs later by MAL in Period 2, MAL followed 4 hrs later by Ralt in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5 |
| FG004 | MAL4Ralt-Ralt-Ralt4MAL-Ralt6MAL-MAL6Ralt | Part 1 was comprised of Periods 1, 2 and 3; Period 3 was followed by a Pause of up to 37 days, before Part 2; Part 2 was comprised of Periods 4 and 5. Each period was separated by a washout of at least 2 days. Each Period had single oral dose treatments as follows: MAL followed 4 hrs later by Ralt in Period 1, Ralt alone in Period 2, Ralt followed 4 hrs later by MAL in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5 |
| FG005 | Ralt4MAL-MAL4Ralt-Ralt-Ralt6MAL-MAL6Ralt | Part 1 was comprised of Periods 1, 2 and 3; Period 3 was followed by a Pause of up to 37 days, before Part 2; Part 2 was comprised of Periods 4 and 5. Each period was separated by a washout of at least 2 days. Each Period had single oral dose treatments as follows: Ralt followed 4 hrs later by MAL in Period 1, MAL followed 4 hrs later by Ralt in Period 2, Ralt alone in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5 |
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| NOT COMPLETED |
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| Part 1 - Period 2 |
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| Part 1 - Period 3 |
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| Pause (up to 37 Days) |
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| Part 2 - Period 4 |
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| Part 2 - Period 5 |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All enrolled participants |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| 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 | Plasma Concentration of Raltegravir at 12 Hours (C 12 Hrs) in Part 1 | Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration. | The per-protocol population consisting of participants from Part 1 only, who complied with the study procedure and had available data from at least one treatment. One participant did not complete one period of Maalox-4 hour-Raltegravir treatment, resulting in an n = 17. | Posted | Geometric Mean | 95% Confidence Interval | nM | 12 hours after dosing on Day 1 of each period |
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| Primary | Area Under the Plasma Concentration Versus Time Curve (AUC 0-12 Hrs) of Raltegravir in Part 1 | Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir in order to determine the geometric mean area under the curve plasma concentration versus time. | The per-protocol population consisting of participants from Part 1 only, who complied with the study procedure and had available data from at least one treatment. One participant did not complete one period of Maalox-4 hour-Raltegravir treatment, resulting in an n = 17. | Posted | Geometric Mean | 95% Confidence Interval | hr.nM | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period |
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| Primary | Maximum Plasma Concentration (C Max) of Raltegravir in Part 1 | Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean maximum plasma concentration. | The per-protocol population consisting of participants from Part 1 only, who complied with the study procedure and had available data from at least one treatment. One participant did not complete one period of Maalox-4 hour-Raltegravir treatment, resulting in an n = 17. | Posted | Geometric Mean | 95% Confidence Interval | nM | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period |
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| Primary | Plasma Concentration of Raltegravir at 12 Hours (C 12 Hrs) in Part 2 | Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration. | The per-protocol population consisting of participants from the Raltegravir alone treatment group from Part 1, and the treatment groups from Part 2, who complied with the study procedure and had available data from at least one treatment. | Posted | Geometric Mean | 95% Confidence Interval | nM | 12 hours after dosing on Day 1 of each period |
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| Primary | Area Under the Plasma Concentration Versus Time Curve (AUC 0-12 Hrs) of Raltegravir in Part 2 | Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean area under the curve plasma concentration versus time. | The per-protocol population consisting of participants from the Raltegravir alone treatment group from Part 1, and the treatment groups from Part 2, who complied with the study procedure and had available data from at least one treatment. | Posted | Geometric Mean | 95% Confidence Interval | hr.nM | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period |
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| Primary | Maximum Plasma Concentration (C Max) of Raltegravir in Part 2 | Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean maximum plasma concentration. | The per-protocol population consisting of participants from the Raltegravir alone treatment group from Part 1, and the treatment groups from Part 2, who complied with the study procedure and had available data from at least one treatment. | Posted | Geometric Mean | 95% Confidence Interval | nM | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1 of each period |
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Up to 84 days
Participants who received at least one dose of the investigational drug. Adverse events are reported not by the sequence of treatments, but rather by the treatment administered at the time of the adverse event.
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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 | Raltegravir | 400 mg Raltegravir alone | 0 | 18 | 0 | 18 | ||
| EG001 | Maalox → 4 Hours → Raltegravir | 20 mL Maalox followed 4 hrs later by 400 mg Raltegravir | 0 | 17 | 1 | 17 | ||
| EG002 | Raltegravir → 4 Hours → Maalox | 400 mg Raltegravir followed 4 hrs later by 20 mL Maalox | 0 | 18 | 1 | 18 | ||
| EG003 | Maalox → 6 Hours → Raltegravir | 20 mL Maalox followed 6 hrs later by 400 mg Raltegravir | 0 | 16 | 2 | 16 | ||
| EG004 | Raltegravir → 6 Hours → Maalox | 400 mg Raltegravir followed 6 hrs later by 20 mL Maalox | 0 | 16 | 0 | 16 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
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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.
| 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 |
| 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 |
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| ID | Term |
|---|---|
| D000068898 | Raltegravir Potassium |
| C013591 | aluminum hydroxide, magnesium hydroxide, drug combination |
| ID | Term |
|---|---|
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Protocol Violation |
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The hypothesis is that the true Raltegravir C 12 hrs GMR is not less than 0.4 |
| Hochberg step-up procedure |
| 0.624 |
| GMR |
| 0.38 |
| 2-Sided |
| 90 |
| 0.30 |
| 0.49 |
The Raltegravir followed by Maalox treatment group was the numerator, and the Raltegravir alone treatment group was the denominator |
| Superiority or Other |
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