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| ID | Type | Description | Link |
|---|---|---|---|
| 38485 | Registry Identifier | DAIDS-ES Registry Number |
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Opening of Arm 2 was dependent upon assessment of DTG pharmacokinetics (PK) data from participants in Arm 1. Arm 1 is complete and results are reported. Arm 2 was not conducted based on the Arm 1 PK assessment.
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| Name | Class |
|---|---|
| ViiV Healthcare | INDUSTRY |
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This study evaluated the potential drug-drug interactions between dolutegravir (DTG) and steady state rifapentine (RPT) when RPT was given with isoniazid (INH) daily for 4 weeks (1HP) as part of treatment for latent TB infection (LTBI) in HIV-1 and LTBI co-infected individuals.
The purpose of this study was to evaluate the potential drug-drug interactions between dolutegravir (DTG) and steady state rifapentine (RPT) when RPT was given with isoniazid (INH) daily for 4 weeks (1HP) as part of treatment for latent TB infection (LTBI) in HIV-1 and LTBI co-infected individuals.
Participants received study-provided INH and RPT once daily for 4 weeks (1HP). During the 1HP treatment, DTG was administered twice daily in Arm 1. Arm 2 planned to administer DTG once daily.
At study entry, all participants were required to be on DTG-based antiretroviral (ARV) treatment with 2 nucleoside reverse transcriptase inhibitors (NRTIs) (tenofovir alafenamide [TAF] was prohibited) during the study. In Arm 1, DTG 50 mg was administered twice daily; the morning dose from non-study ARV supply and the evening dose from study supply.
Participants were also required to receive pyridoxine (vitamin B6) with each dose of INH based on the current local, national, or international dosing guidelines. NRTI therapy and pyridoxine (vitamin B6) was not provided by the study.
The majority of Arm 1 participants were on study for 6 weeks (a 4-week on-study treatment period and a 2-week follow-up period). Arm 1 participants could be on study for up to 11 weeks if the on-study treatment duration was extended or if participants needed additional follow-up visits to measure viral load.
The study began enrollment with Arm 1. Opening of Arm 2 was dependent upon assessment of DTG pharmacokinetics (PK) data from participants in Arm 1.
Arm 1 is complete and results are reported. Arm 2 was not conducted based on the Arm 1 PK assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: DTG + INH + RPT | Experimental | Participants received 50 mg of DTG orally twice daily (~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks. Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH. Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. |
|
| Arm 2: DTG + INH + RPT | Experimental | Participants were to receive 50 mg of DTG orally each morning and 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks. Participants were also to have received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH. Participants were to remain on once-daily DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study with DTG supplied from non-study ARV supply. It was decided to not move forward with Arm 2 of the study based on the Arm 1 PK assessment and no participants were enrolled in Arm 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dolutegravir (DTG) | Drug | Administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| DTG PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on DTG Levels From Individual Participants in Arm 1 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter Cmax obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). Cmax defines the model-predicted maximum concentration observed over the 12- or 24- hours of the DTG dosing interval. | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28 |
| DTG PK Parameter Area Under the Concentration Time Curve (AUC0-24) Calculated Based on Intensive PK Samples Obtained From Individual Participants Enrolled in Arm 1 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter AUC 0-24h obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). AUC 0-24h defines area under the concentration-time curve over the period of 24 hours post-dose estimated based on the fitted model. For Arm 1, Day 28 (BID dosing), participant-specific AUC0-24h was estimated by summing participant-specific estimated AUC values for the 0-12 hour dosing interval (AUC0-12). | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28 |
| DTG PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on DTG Levels From Individual Participants in Arm 1 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter Cmin obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). Cmin defines the model-predicted minimum concentration observed over the 12- or 24- hour DTG dosing interval. | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28 |
| DTG PK Parameter Ctrough Determined Based on DTG Levels From Individual Participants in Arm 1 at Day 28 | This evaluates the effect of RPT on the DTG PK parameter Ctrough obtained from participants enrolled in Arm 1 at day 28 (DTG BID with 1HP). Ctrough defines the observed non-model based minimum concentration observed over the 12- hour DTG dosing interval. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants in Arm 1 With an Occurrence of Grade 2 or Higher Adverse Event | Arm 1 participants with an occurrence of an adverse event (laboratory value, sign/symptom, diagnosis) of grade 2 or higher on a scale of 1 to 5 where 5 is the most severe. Severity graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Participants were counted once at the highest grade. |
Not provided
Inclusion Criteria:
Ability and willingness of participant or legal guardian/representative to provide informed consent.
Weight ≥40 kg and a body mass index (BMI) of greater than 18.5 kg/m^2.
Documentation of HIV-1 infection status, as below:
HIV-1 plasma viral load <50 copies/mL obtained within 30 days prior to study entry by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that is Virology Quality Assessment (VQA) certified.
At US sites: Evidence of LTBI by tuberculin skin test (TST) reactivity ≥5 mm, or a positive interferon gamma release assay (IGRA) at any time prior to study entry.
On a stable once daily DTG (50 mg) based ART with once daily 2 NRTIs and
Chest radiograph or chest computed tomography (CT) scan performed within 30 days prior to study entry without evidence of active TB.
The following laboratory values obtained within 30 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent, or at any network approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practice (GCLP) and participates in appropriate external quality assurance programs.
For females of reproductive potential, negative serum or urine pregnancy test at Screening within 30 days prior to entry and within 48 hours prior to entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs.
Female participants of reproductive potential must agree not to participate in the conception process (i.e., active attempt to become pregnant, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, must agree to use one reliable nonhormonal method of contraception, as listed below, while on study treatment and through study completion.
Acceptable forms of contraception include:
Exclusion Criteria:
Breastfeeding, pregnancy, or plans to become pregnant.
Known allergy/sensitivity or any hypersensitivity to components of the study drugs, or their formulations.
Presence of any confirmed or probable active TB based on criteria listed in the current AIDS Clinical Trials Group (ACTG) Diagnosis Appendix at screening.
History of rifamycin-monoresistant, INH-monoresistant, multi-drug resistant (MDR) or extensively-drug resistant (XDR) TB at any time prior to study entry
Known exposure to rifamycin-monoresistant, INH-monoresistant, MDR- or XDR-TB (e.g., household member of a person with rifamycin-monoresistant, INH monoresistant, MDR- or XDR-TB) at any time prior to study entry by participant self report or medical records.
History of peripheral neuropathy Grade ≥2 according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, July 2017, which can be found on the DAIDS RSC website at https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables.
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Acute or serious illness requiring systemic treatment and/or hospitalization within 7 days prior to study entry.
Known cirrhosis, a history of decompensated liver disease (ascites, hepatic encephalopathy, or esophageal varices) or current Child Pugh Class B or C hepatic impairment.
Initiated, discontinued, or changed doses of drugs that are P-glycoprotein (PGP) inducers, that are P-glycoprotein (PGP) inhibitors,or that are known to have drug interactions with DTG, within 30 days prior to study entry.
Known porphyria at any time prior to study entry.
Receipt of any other antiretroviral therapy other than DTG and 2 NRTI within 28 days prior to study entry.
Receipt of TAF within 28 days prior to study entry.
Documented resistance that may confer reduced susceptibility to DTG, at any time prior to study entry. This includes the following INSTI mutations: Q148 substitutions, T66A, L74I/M, E138A/K/T, G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, G193E/R, or N155H.
Clinically suspected INSTI resistance, at any time prior to study entry, as evidenced by prior receipt of INSTI containing ART, during which time two or more HIV-1 RNA levels of >200 copies/mL were observed after having attained virologic suppression to <200 copies/mL and without known interruption.
Consumption of >3 alcohol beverages on any day within 30 days prior to entry.
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| Name | Affiliation | Role |
|---|---|---|
| Anthony Podany, PharmD | University of Nebraska | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California HIV/AIDS CRS | San Francisco | California | 94110 | United States | ||
| Houston AIDS Research Team CRS |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38568956 | Derived | Podany AT, Cramer Y, Imperial M, Rosenkranz SL, Avihingsanon A, Arduino R, Samaneka W, Gelmanova I, Savic R, Swindells S, Dawson R, Luetkemeyer AF. Twice-Daily Dolutegravir-Based Antiretroviral Therapy With 1 Month of Daily Rifapentine and Isoniazid for Tuberculosis Prevention. Clin Infect Dis. 2024 Oct 15;79(4):983-989. doi: 10.1093/cid/ciae183. |
| Label | URL |
|---|---|
| Location of Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 | View source |
Not provided
Individual participant data that underlie results in the publication, after deidentification.
Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
With whom?
For what types of analyses?
By what mechanism will data be made available?
Not provided
Participants were not randomized and enrollment was not stratified. To create by-country diversity of participants, screening and accrual limits were set for US and non-US sites.
Participants in Arm 1 were enrolled from February 2021 to November 2021 at 9 selected US and non-US ACTG clinical research sites. It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2. Results are for Arm 1 only.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: DTG + INH + RPT | Participants received 50 mg of DTG orally twice daily (~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks. Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH. Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. Dolutegravir (DTG): Administered orally Isoniazid (INH): Administered orally Rifapentine (RPT): Administered orally Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply. Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_ICF | Yes | No | Yes | Study Protocol and Informed Consent Form | Jun 11, 2021 |
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| Isoniazid (INH) | Drug | Administered orally |
|
| Rifapentine (RPT) | Drug | Administered orally |
|
| Antiretroviral Therapy (ART) | Drug | Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply. |
|
| Pyridoxine (Vitamin B6) | Dietary Supplement | Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study. |
|
| Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at day 28 |
| DTG PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on DTG Levels From Individual Participants in Arm 2 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter Cmax obtained from participants enrolled in Arm 2 at day 0 (DTG QD) and day 28 (DTG QD with 1HP). Cmax defines the model-predicted maximum concentration observed over the 24- hours of the DTG dosing interval. | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28 |
| DTG PK Parameter Area Under the Concentration Time Curve (AUC0-24) Calculated Based on Intensive PK Samples Obtained From Individual Participants Enrolled in Arm 2 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter AUC 0-24h obtained from participants enrolled in Arm 2 at day 0 (DTG QD) and day 28 (DTG QD with 1HP). AUC 0-24h defines area under the concentration-time curve over the period of 24 hours post-dose estimated based on the fitted model. | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28 |
| DTG PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on DTG Levels From Individual Participants in Arm 2 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter Cmin obtained from participants enrolled in Arm 2 at day 0 (DTG QD) and day 28 (DTG QD with 1HP). Cmin defines the model-predicted minimum concentration observed over the 24- hour DTG dosing interval. | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28 |
| DTG PK Parameter Ctrough Determined Based on DTG Levels From Individual Participants in Arm 2 at Day 28 | This evaluates the effect of RPT on the DTG PK parameter Ctrough obtained from participants enrolled in Arm 2 at day 28 (DTG QD with 1HP). Ctrough defines the observed non-model based minimum concentration observed over the 24- hour DTG dosing interval. | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28 |
| From initiation of study treatment to day 28 |
| Percentage of Participants in Arm 1 Who Completed the Study | Percentage of participants in Arm 1 who completed the study | From initiation of study to day 28 |
| Percentage of Participants in Arm 1 Who Completed Study Drug Treatment | Percentage of participants in Arm 1 who completed study drug treatment (DTG+1HP) | From initiation of study treatment to day 28 |
| Percentage of Participants in Arm 1 With HIV-1 RNA Levels >50 Copies/mL | This evaluates the short-term impact on virologic suppression of DTG based ART when coadministered with 1HP by measuring the percentage of participants with plasma HIV-1 RNA levels >50 copies/mL at study day 28 (after 4 weeks of DTG+1HP) and study day 42 (14 days after completing study treatment). | Measured at Days 28 and 42 |
| Percentage of Participants in Arm 2 With an Occurrence of Grade 2 or Higher Adverse Event | Arm 2 participants with an occurrence of an adverse event (laboratory value, sign/symptom, diagnosis) of grade 2 or higher on a scale of 1 to 5 where 5 is the most severe. Severity graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Participants will be counted once at the highest grade. | From initiation of study treatment to day 28 |
| Percentage of Participants in Arm 2 Who Completed the Study | Percentage of participants in Arm 2 who completed the study. | From initiation of study to day 28 |
| Percentage of Participants in Arm 2 Who Completed Study Drug Treatment | Percentage of participants in Arm 2 who completed study drug treatment (DTG+1HP). | From initiation of study treatment to day 28 |
| Percentage of Participants in Arm 2 With HIV-1 RNA Levels >50 Copies/mL | This evaluates the short-term impact on virologic suppression of DTG based ART when coadministered with 1HP by measuring the percentage of participants with plasma HIV-1 RNA levels >50 copies/mL at study day 28 (after 4 weeks of DTG+1HP) and study day 42 (14 days after completing study treatment). | Measured at Days 28 and 42 |
| Houston |
| Texas |
| 77030 |
| United States |
| Gaborone CRS | Gaborone | South-East District | Botswana |
| GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS | Port-au-Prince | HT-6110 | Haiti |
| Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS | Port-au-Prince | HT-6110 | Haiti |
| Malawi CRS | Lilongwe | Central Malawi | Malawi |
| University of Cape Town Lung Institute (UCTLI) CRS | Cape Town | 7700 | South Africa |
| South African Tuberculosis Vaccine Initiative (SATVI) CRS | Cape Town | 7705 | South Africa |
| Thai Red Cross AIDS Research Centre (TRC-ARC) CRS | Pathum Wan | Bangkok | 10330 | Thailand |
| Milton Park CRS | Milton Park | Harare | Zimbabwe |
| COMPLETED |
|
| NOT COMPLETED |
|
|
All participants who enrolled to the study
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1: DTG + INH + RPT | Participants received 50 mg of DTG orally twice daily (~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks. Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH. Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. Dolutegravir (DTG): Administered orally Isoniazid (INH): Administered orally Rifapentine (RPT): Administered orally Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply. Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by 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 | Median | Inter-Quartile Range | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| |||||||||||||||||||||||
| HIV-1 RNA below 50 copies/mL | Count of Participants | Participants |
|
| 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 | DTG PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on DTG Levels From Individual Participants in Arm 1 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter Cmax obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). Cmax defines the model-predicted maximum concentration observed over the 12- or 24- hours of the DTG dosing interval. | All Arm 1 participants who initiated the 1HP TB regimen, who completed 28 daily doses RPT/INH within the 6-week study period, and who took DTG twice-daily for days 1-28. Sampling took place after ensuring 3 days of consecutive DTG QD dosing prior to day 0, and 3 days of consecutive DTG BID with 1HP dosing prior to Day 28. | Posted | Median | Inter-Quartile Range | ng/mL | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28 |
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|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | DTG PK Parameter Area Under the Concentration Time Curve (AUC0-24) Calculated Based on Intensive PK Samples Obtained From Individual Participants Enrolled in Arm 1 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter AUC 0-24h obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). AUC 0-24h defines area under the concentration-time curve over the period of 24 hours post-dose estimated based on the fitted model. For Arm 1, Day 28 (BID dosing), participant-specific AUC0-24h was estimated by summing participant-specific estimated AUC values for the 0-12 hour dosing interval (AUC0-12). | All Arm 1 participants who initiated the 1HP TB regimen, who completed 28 daily doses RPT/INH within the 6-week study period, and who took DTG twice-daily for days 1-28. Sampling took place after ensuring 3 days of consecutive DTG QD dosing prior to day 0, and 3 days of consecutive DTG BID with 1HP dosing prior to Day 28. | Posted | Median | Inter-Quartile Range | h*ng/mL | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28 |
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| Primary | DTG PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on DTG Levels From Individual Participants in Arm 1 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter Cmin obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). Cmin defines the model-predicted minimum concentration observed over the 12- or 24- hour DTG dosing interval. | All Arm 1 participants who initiated the 1HP TB regimen, who completed 28 daily doses RPT/INH within the 6-week study period, and who took DTG twice-daily for days 1-28. Sampling took place after ensuring 3 days of consecutive DTG QD dosing prior to day 0, and 3 days of consecutive DTG BID with 1HP dosing prior to Day 28. | Posted | Median | Inter-Quartile Range | ng/mL | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28 |
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| Primary | DTG PK Parameter Ctrough Determined Based on DTG Levels From Individual Participants in Arm 1 at Day 28 | This evaluates the effect of RPT on the DTG PK parameter Ctrough obtained from participants enrolled in Arm 1 at day 28 (DTG BID with 1HP). Ctrough defines the observed non-model based minimum concentration observed over the 12- hour DTG dosing interval. | All Arm 1 participants who initiated the 1HP TB regimen, who completed 28 daily doses RPT/INH within the 6-week study period, and who took DTG twice-daily for days 1-28. Sampling took place after ensuring 3 days of consecutive DTG QD dosing prior to day 0, and 3 days of consecutive DTG BID with 1HP dosing prior to Day 28. | Posted | Median | Inter-Quartile Range | ng/mL | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at day 28 |
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| Primary | DTG PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on DTG Levels From Individual Participants in Arm 2 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter Cmax obtained from participants enrolled in Arm 2 at day 0 (DTG QD) and day 28 (DTG QD with 1HP). Cmax defines the model-predicted maximum concentration observed over the 24- hours of the DTG dosing interval. | It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2. | Posted | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28 |
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| Primary | DTG PK Parameter Area Under the Concentration Time Curve (AUC0-24) Calculated Based on Intensive PK Samples Obtained From Individual Participants Enrolled in Arm 2 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter AUC 0-24h obtained from participants enrolled in Arm 2 at day 0 (DTG QD) and day 28 (DTG QD with 1HP). AUC 0-24h defines area under the concentration-time curve over the period of 24 hours post-dose estimated based on the fitted model. | It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2. | Posted | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28 |
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| Primary | DTG PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on DTG Levels From Individual Participants in Arm 2 by Visit Day | This evaluates the effect of RPT on the DTG PK parameter Cmin obtained from participants enrolled in Arm 2 at day 0 (DTG QD) and day 28 (DTG QD with 1HP). Cmin defines the model-predicted minimum concentration observed over the 24- hour DTG dosing interval. | It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2. | Posted | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28 |
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| Primary | DTG PK Parameter Ctrough Determined Based on DTG Levels From Individual Participants in Arm 2 at Day 28 | This evaluates the effect of RPT on the DTG PK parameter Ctrough obtained from participants enrolled in Arm 2 at day 28 (DTG QD with 1HP). Ctrough defines the observed non-model based minimum concentration observed over the 24- hour DTG dosing interval. | It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2. | Posted | Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28 |
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| Secondary | Percentage of Participants in Arm 1 With an Occurrence of Grade 2 or Higher Adverse Event | Arm 1 participants with an occurrence of an adverse event (laboratory value, sign/symptom, diagnosis) of grade 2 or higher on a scale of 1 to 5 where 5 is the most severe. Severity graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Participants were counted once at the highest grade. | Participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG. | Posted | Number | 95% Confidence Interval | Percentage of participants | From initiation of study treatment to day 28 |
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| Secondary | Percentage of Participants in Arm 1 Who Completed the Study | Percentage of participants in Arm 1 who completed the study | Participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG. | Posted | Number | 95% Confidence Interval | Percentage of participants | From initiation of study to day 28 |
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| Secondary | Percentage of Participants in Arm 1 Who Completed Study Drug Treatment | Percentage of participants in Arm 1 who completed study drug treatment (DTG+1HP) | Participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG. | Posted | Number | 95% Confidence Interval | Percentage of participants | From initiation of study treatment to day 28 |
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| Secondary | Percentage of Participants in Arm 1 With HIV-1 RNA Levels >50 Copies/mL | This evaluates the short-term impact on virologic suppression of DTG based ART when coadministered with 1HP by measuring the percentage of participants with plasma HIV-1 RNA levels >50 copies/mL at study day 28 (after 4 weeks of DTG+1HP) and study day 42 (14 days after completing study treatment). | All participants in who took at least one dose of study drugs and who had HIV-1 RNA data available. | Posted | Number | percentage of participants | Measured at Days 28 and 42 |
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| Secondary | Percentage of Participants in Arm 2 With an Occurrence of Grade 2 or Higher Adverse Event | Arm 2 participants with an occurrence of an adverse event (laboratory value, sign/symptom, diagnosis) of grade 2 or higher on a scale of 1 to 5 where 5 is the most severe. Severity graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Participants will be counted once at the highest grade. | It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2. | Posted | From initiation of study treatment to day 28 |
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| Secondary | Percentage of Participants in Arm 2 Who Completed the Study | Percentage of participants in Arm 2 who completed the study. | It was decided to not move forward with Arm2 of the study and no participants were enrolled in Arm 2. | Posted | From initiation of study to day 28 |
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| Secondary | Percentage of Participants in Arm 2 Who Completed Study Drug Treatment | Percentage of participants in Arm 2 who completed study drug treatment (DTG+1HP). | It was decided to not move forward with Arm2 of the study and no participants were enrolled in Arm 2. | Posted | From initiation of study treatment to day 28 |
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| Secondary | Percentage of Participants in Arm 2 With HIV-1 RNA Levels >50 Copies/mL | This evaluates the short-term impact on virologic suppression of DTG based ART when coadministered with 1HP by measuring the percentage of participants with plasma HIV-1 RNA levels >50 copies/mL at study day 28 (after 4 weeks of DTG+1HP) and study day 42 (14 days after completing study treatment). | It was decided to not move forward with Arm2 of the study and no participants were enrolled in Arm 2. | Posted | Measured at Days 28 and 42 |
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From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1: DTG + INH + RPT | Participants received 50 mg of DTG orally twice daily (~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks. Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH. Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. Dolutegravir (DTG): Administered orally Isoniazid (INH): Administered orally Rifapentine (RPT): Administered orally Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply. Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study. | 0 | 36 | 0 | 36 | 15 | 36 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 26.1 | Systematic Assessment |
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| Conjunctivitis allergic | Eye disorders | MedDRA 26.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 26.1 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
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| Orchitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 26.1 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA 26.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 26.1 | Systematic Assessment |
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| Glomerular filtration rate decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA 26.1 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 26.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 26.1 | Systematic Assessment |
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In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| ACTG Clinicaltrials.gov Coordinator | ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company | (301) 628-3348 | ACTGCT.gov@fstrf.org |
| Jul 16, 2024 |
| Prot_ICF_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 7, 2021 | Apr 4, 2024 | SAP_001.pdf |
Not provided
| 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 |
Not provided
Not provided
| ID | Term |
|---|---|
| C562325 | dolutegravir |
| D007538 | Isoniazid |
| C018421 | rifapentine |
| D023241 | Antiretroviral Therapy, Highly Active |
| D011736 | Pyridoxine |
| D025101 | Vitamin B 6 |
| ID | Term |
|---|---|
| D006834 | Hydrazines |
| D009930 | Organic Chemicals |
| D007539 | Isonicotinic Acids |
| D000147 | Acids, Heterocyclic |
| D006571 | Heterocyclic Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D004359 | Drug Therapy, Combination |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D010847 | Picolines |
Not provided
Not provided
| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Malawi |
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| Botswana |
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| South Africa |
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| Zimbabwe |
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| Thailand |
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