Pharmacokinetic Study to Evaluate Double-Dose Levonorgestrel Emergency Contraception in Combination With Efavirenz-Based Antiretroviral Therapy or Rifampicin-Containing Anti-Tuberculosis Therapy
Study Details
Study Description
Brief Summary
The purpose of this pharmacokinetic (PK) study was to evaluate if a double dose (3 mg) of levonorgestrel (LNG) overcomes known drug-drug interactions (DDIs) with efavirenz (EFV)-based antiretroviral therapy (ART) or rifampicin (RIF)-containing tuberculosis (TB) therapy. The safety of double-dose (3.0 mg) LNG versus standard-dose (1.5 mg) was also compared.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This pharmacokinetic (PK) study evaluated if a double dose (3.0 mg) of levonorgestrel (LNG) overcomes known drug-drug interactions (DDIs) with efavirenz (EFV)-based antiretroviral therapy (ART) or rifampicin (RIF)-containing tuberculosis (TB) therapy. The safety of double-dose (3.0 mg) LNG versus standard-dose (1.5 mg) was also compared.
Participants were volunteers who did not require emergency contraception (EC) for contraception at the time of trial participation. This trial enrolled persons assigned female sex at birth who were 16 years of age or older. Group assignment was determined by disease status (HIV or TB; participants could not have been living with both HIV and TB), and, for those with HIV, by ART regimen at enrollment. Participants with HIV who were taking EFV-based ART were randomized to receive a standard dose LNG (Group A) or a double dose of LNG (Group B). Participants taking dolutegravir (DTG)-based ART were assigned to a standard dose of LNG (Group C). Participants in the continuation phase of active TB treatment taking RIF and isoniazid (INH) with or without ethambutol were assigned to a double dose of LNG (Group D).
At study entry, participants in Groups A and C received a standard single dose of LNG. Participants in Groups B and D received a double dose of LNG. Intensive PK monitoring was conducted pre-dose, and after the LNG dose. Participants were expected to remain at the clinical site while the initial 8 hour PK samples were collected, and to return to the clinical site for the 24 and 48 hour samples.
All participants completed self-report questionnaires to assess adherence to TB therapy and ART, menstrual history and patterns after LNG administration, and to collect adverse effects commonly reported with LNG (i.e., irregular bleeding patterns). Adherence to ART and RIF was also assessed by collecting hair samples and single plasma concentrations at entry. Participants were followed for 4 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A: LNG 1.5 mg among participants on EFV-based ART (randomized) Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
Drug: Levonorgestrel (LNG)
LNG tablet(s) were administered by mouth in a directly observed manner.
|
| Experimental: B: LNG 3.0 mg among participants on EFV-based ART (randomized) Participants received 3mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
Drug: Levonorgestrel (LNG)
LNG tablet(s) were administered by mouth in a directly observed manner.
|
| Experimental: C: LNG 1.5 mg among participants on DTG-based ART (assigned) Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
Drug: Levonorgestrel (LNG)
LNG tablet(s) were administered by mouth in a directly observed manner.
|
| Experimental: D: LNG 3.0 mg among participants on RIF-INH TB Therapy (assigned) Participants received 3mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
Drug: Levonorgestrel (LNG)
LNG tablet(s) were administered by mouth in a directly observed manner.
|
Outcome Measures
Primary Outcome Measures
- LNG Area Under the Concentration-time Curve (AUC0-8h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants [Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose]
AUC for each participant was calculated from all available LNG concentrations measured over 8 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification (LLOQ) for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).
Secondary Outcome Measures
- Number and Percentage of Participants Experiencing Either a Serious Adverse Event (SAE) or Adverse Event (AE) Potentially or Definitely Associated With Single Dose LNG Administration. [From Day 0 through study Day 28]
Adverse events were 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 and DAIDS AE Grading Table Addendum 1, Female Genital Grading Table for Use in Microbicide Studies, Version 1.0 - November 2007. Relationship of AE to study treatment was determined by the site, study core team, and DAIDS clinical representative. AEs evaluated in this outcome fulfilled the below criteria: Potentially or definitely related to LNG dose Grade 3 or higher AEs Grade 2 of higher nausea, diarrhea, menorrhagia or metrorrhagia, and ectopic pregnancies
- Maximum Concentration (Cmax) of LNG [Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose]
Cmax for each participant was calculated as the maximum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmax using the software package Phoenix WinNonLin (Certara®).
- Minimum Concentration (Cmin) of LNG [Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose]
Cmin for each participant was calculated as the minimum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmin using the software package Phoenix WinNonLin (Certara®). Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).
- Oral Clearance (CL/F) of LNG [Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose]
Apparent oral clearance (CL/F) for each participant was calculated as CL/F = dose/AUC0-24 or CL/F = dose/AUC0-48 of the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine CL/F using the software package Phoenix WinNonLin (Certara®).
- Volume of Distribution (Vd) of LNG [Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose]
Vd for each participant was calculated from observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Vd using the software package Phoenix WinNonLin (Certara®).
- Half-life (T1/2) of LNG [Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose]
T1/2 for each participant was calculated using regression analysis when possible from the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine T1/2 using the software package Phoenix WinNonLin (Certara®).
- Time of Minimum Concentration (Tmin) of LNG [Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose]
Tmin for each participant was time to the minimum observed LNG concentration after the observed dose.
- LNG Area Under the Concentration Time Curve (AUC0-24h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants [Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours post-dose]
AUC for each participant was calculated from all available LNG concentrations measured over 24 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).
- LNG Area Under the Concentration Time Curve (AUC0-48h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants [Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose]
AUC for each participant was calculated from all available LNG concentrations measured over 48 hours using the linear up/log down version of the trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).
- LNG Total Area Under the Concentration Time Curve AUCinf (Infinity) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants [Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose]
AUC for each participant was calculated from all available LNG concentrations measured to infinity hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Postmenarcheal female.
-
Note: Participant report and clinician's opinion were acceptable.
-
The following laboratory values obtained within 30 days prior to study entry by any US laboratory that had a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any ACTG network-approved non-US laboratory that operated in accordance with Good Clinical Laboratory Practices (GCLP) and participated in appropriate external quality assurance (EQA) programs.
-
Absolute neutrophil count (ANC) greater than or equal to 500 cells/mm^3
-
Platelet count greater than or equal to 50,000 platelets/mm^3
-
Hemoglobin greater than or equal to 8.0 g/dL
-
Aspartate transaminase (AST) less than 5 x upper limit of normal (ULN)
-
Alanine aminotransferase (ALT) less than 5 x ULN
-
Creatinine less than or equal to 1.5 x ULN
-
Total bilirubin less than or equal to 2.0 x ULN
-
Negative serum or urine pregnancy test within 30 days prior to study entry and within 48 hours prior to entry (if screening occurred more than 48 hours prior to entry) by any US clinic or US laboratory that had a CLIA certification or its equivalent, or used a point of care (POC)/CLIA-waived test, or at any network-approved non-US laboratory or non-US clinic that operated in accordance with GCLP and participated in appropriate EQA programs. The serum or urine pregnancy test must have had a sensitivity of at least 25 mIU/mL.
-
Had not had sex that could lead to pregnancy without contraception within 14 days prior to study entry as defined in the criteria below, according to participant self-report.
-
Contraception requirements
-
All participants agreed not to participate in a conception process (e.g., active attempt to become pregnant or in vitro fertilization) for the duration of the study. Women of reproductive potential, who were participating in sexual activity that could lead to pregnancy, agreed to use at least one reliable method of contraception while in the study. Acceptable forms of contraceptives included:
-
Male condom with or without a spermicidal agent
-
Diaphragm or cervical cap with spermicide
-
Non-hormonal intrauterine device (IUD)
-
Bilateral tubal ligation
-
Male partner vasectomy
-
Ability and willingness of participant or legal guardian/representative to have provided informed consent.
-
Body mass index (BMI) (kg/m^2) available at entry. See the study protocol for BMI calculation instructions.
-
Note: A maximum of 5 participants with BMI greater than or equal to 30 kg/m^2 were allowed in each arm B-D and a maximum of 3 participants in Arm A.
-
For participants with HIV: HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
-
Note: The term "licensed" referred to a US Food and Drug Administration (FDA)-approved kit, which was required for all investigational new drug (IND) studies, or for sites located in countries other than the United States, a kit that had been certified or licensed by an oversight body within that country and validated internally. Non-US sites were encouraged to use US FDA-approved methods for IND studies.
-
World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) guidelines mandated that confirmation of the initial test result must have used a test that was different from the one used for the initial assessment. A reactive initial rapid test was confirmed by either another type of rapid assay or an E/CIA that was based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
-
For participants with HIV: Received a stable qualifying concomitant ART regimen containing either once-daily DTG 50 mg or EFV 600 mg with no changes in the components of their ART for at least 30 days prior to study entry.
-
For participants who were being treated for TB: HIV-negative at screening, documented within the prior 6 months by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load.
-
Note: The term "licensed" referred to a US FDA-approved kit, which was required for all IND studies, or for sites located in countries other than the United States, a kit that had been certified or licensed by an oversight body within that country and validated internally. Non-US sites were encouraged to use US FDA-approved methods for IND studies.
-
WHO and CDC guidelines mandated that confirmation of the initial test result must have used a test that was different from the one used for the initial assessment. A reactive initial rapid test was confirmed by either another type of rapid assay or an E/CIA that was based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
-
For participants who were living without HIV and being treated for TB: Received RIF and INH on a once daily dosing (7 days per week) schedule at study entry, after completion of the intensive phase of TB treatment.
-
Note: Inclusion of ethambutol as part of continuation phase of TB therapy was allowed.
-
Ability and willingness of participant to have been contacted remotely for study visits.
Exclusion Criteria
-
Known allergy/sensitivity or any hypersensitivity to LNG or components of the formulation.
-
Bilateral oophorectomy, hysterectomy, or postmenopausal
-
Note: Postmenopausal was defined as amenorrhea for at least 12 consecutive months prior to study entry (in the absence of medications known to induce amenorrhea), and had a documented follicle stimulated hormone-release factor (FSH) measurement greater than 40 mIU/mL or a result in the testing laboratory's menopausal range. If an FSH level was not available, 24 consecutive months of amenorrhea prior to study entry (in the absence of medications known to induce amenorrhea).
-
Note: Clinical assessment and clinician's opinion were acceptable.
-
Was currently pregnant, was within 6 weeks of delivery, or was currently breastfeeding an infant under 6 months of age.
-
Note: For recent pregnancy resolution during the first or second trimester, the participant was only eligible when the pregnancy test result was negative.
-
Receipt of LNG within 30 days prior to study entry.
-
Receipt of depo-medroxyprogesterone for 90 days prior to study entry, or norethisterone enanthate (NET-EN) within 60 days prior to study entry, or other hormonal contraceptives within 30 days prior to study entry.
-
Used any drugs other than RIF and EFV known to: 1) induce CYP3A4 system within 30 days prior to study entry, and 2) inhibit the CYP3A4 system within 7 days prior to study entry. See the study protocol for prohibited and precautionary medications.
-
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would have interfered with adherence to study requirements.
-
Acute or serious illness that required systemic treatment and/or hospitalization within 14 days prior to study entry.
-
Other medical, psychiatric, or psychological condition that, in the opinion of the site investigator, would have interfered with completion of study procedures and or adherence to study drug.
-
For participants with HIV: Was currently receiving medications for TB infection.
-
For participants with HIV: Had missed one or more of the prescribed doses of HIV medications within 3 days prior to study entry.
-
Note: The entry visit could have been rescheduled within the screening period once the participant had taken all prescribed doses within 3 days prior to study entry.
-
For participants who were not living with HIV and were being treated for TB: Had missed one or more of the prescribed doses of TB medication within 3 days prior to study entry.
-
Note: The entry visit could have been rescheduled within the screening period once the participant had taken all prescribed doses within 3 days prior to study entry.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 2701 Northwestern University CRS | Chicago | Illinois | United States | 60611 |
| 2 | Rush Univ. Med. Ctr. ACTG CRS (2702) | Chicago | Illinois | United States | 60612 |
| 3 | Weill Cornell Upton CRS (7803) | New York | New York | United States | 10065 |
| 4 | Unc Aids Crs (3201) | Chapel Hill | North Carolina | United States | 27514 |
| 5 | Hosp. of the Univ. of Pennsylvania CRS (6201) | Philadelphia | Pennsylvania | United States | 19104 |
| 6 | Pitt CRS (1001) | Pittsburgh | Pennsylvania | United States | 15213 |
| 7 | Trinity Health and Wellness Center CRS (31443) | Dallas | Texas | United States | 75208 |
| 8 | Gaborone CRS (12701) | Gaborone | Botswana | ||
| 9 | 12101 Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS | Rio de Janeiro | Brazil | 21040 | |
| 10 | Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS (12501) | Kericho | Kenya | 20200 | |
| 11 | Blantyre CRS (30301) | Blantyre | Malawi | ||
| 12 | Malawi CRS (12001) | Lilongwe | Malawi | ||
| 13 | University of the Witwatersrand Helen Joseph (WITS HJH) CRS (11101) | Johannesburg | Gauteng | South Africa | 2193 |
| 14 | Family Clinical Research Unit (FAM-CUR) CRS (8950) | Cape Town | West Cape | South Africa | 7505 |
| 15 | Durban Adult HIV CRS (11201) | Durban | South Africa | 4013 SF | |
| 16 | Soweto ACTG CRS (12301) | Johannesburg | South Africa | ||
| 17 | 31802 Thai Red Cross AIDS Research Centre (TRC-ARC) CRS | Bangkok | Patumwan | Thailand | 10330 |
| 18 | 31784 Chiang Mai University HIV Treatment CRS | Chiang Mai | Thailand | 50200 |
Sponsors and Collaborators
- AIDS Clinical Trials Group
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Study Chair: Kimberly Scarsi, PharmD, MS, Northwestern University CRS, University of Nebraska Medical Center
Study Documents (Full-Text)
More Information
Additional Information:
- The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.1, July 2017.
- Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010
- DAIDS AE Grading Table Addendum 1, Female Genital Grading Table for Use in Microbicide Studies, Version 1.0, November 2007
Publications
None provided.- ACTG A5375
- 38493
- UM1AI068636
Study Results
Participant Flow
| Recruitment Details | Participants enrolled from 18 sites. Sites were located in the United States and internationally (Botswana, Brazil, Kenya, Malawi, South Africa, Thailand). The first participant accrued in May 2019, and the last participant accrued in November 2020. |
|---|---|
| Pre-assignment Detail | Participants receiving EFV-based ART therapy were randomized between Group A (1.5mg dose of LNG) and Group B (3.0mg dose of LNG) in a 1:2 ratio using permuted blocks and institutional balancing. Participants living with HIV receiving DTG-based ART therapy and participants with TB receiving RIF-INH therapy were assigned to study groups C and D, respectively. Women with BMI greater than or equal to 30 kg/m2 were limited to no more than 5 within Groups B-D and no more than three within Group A. |
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Period Title: Overall Study | ||||
| STARTED | 17 | 36 | 35 | 34 |
| Received LNG Treatment | 17 | 36 | 35 | 34 |
| COMPLETED | 17 | 35 | 33 | 34 |
| NOT COMPLETED | 0 | 1 | 2 | 0 |
Baseline Characteristics
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Total of all reporting groups |
| Overall Participants | 17 | 35 | 32 | 34 | 118 |
| Age (years) [Median (Inter-Quartile Range) ] | |||||
| Median (Inter-Quartile Range) [years] |
42
|
36
|
34
|
25
|
34
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
17
100%
|
35
100%
|
32
100%
|
34
100%
|
118
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| Asian |
9
52.9%
|
20
57.1%
|
2
6.3%
|
2
5.9%
|
33
28%
|
| Black (Non-Hispanic) |
7
41.2%
|
12
34.3%
|
24
75%
|
30
88.2%
|
73
61.9%
|
| Hispanic or Latino (Regardless of race) |
1
5.9%
|
3
8.6%
|
4
12.5%
|
2
5.9%
|
10
8.5%
|
| Multiple Races |
0
0%
|
0
0%
|
1
3.1%
|
0
0%
|
1
0.8%
|
| White (Non-Hispanic) |
0
0%
|
0
0%
|
1
3.1%
|
0
0%
|
1
0.8%
|
| Region of Enrollment (Count of Participants) | |||||
| Botswana |
0
0%
|
0
0%
|
0
0%
|
2
5.9%
|
2
1.7%
|
| Brazil |
1
5.9%
|
3
8.6%
|
4
12.5%
|
2
5.9%
|
10
8.5%
|
| Kenya |
0
0%
|
0
0%
|
0
0%
|
4
11.8%
|
4
3.4%
|
| Malawi |
0
0%
|
0
0%
|
10
31.3%
|
6
17.6%
|
16
13.6%
|
| South Africa |
7
41.2%
|
12
34.3%
|
2
6.3%
|
18
52.9%
|
39
33.1%
|
| Thailand |
9
52.9%
|
20
57.1%
|
2
6.3%
|
2
5.9%
|
33
28%
|
| United States |
0
0%
|
0
0%
|
14
43.8%
|
0
0%
|
14
11.9%
|
| Gender Identity (Count of Participants) | |||||
| Cisgender |
17
100%
|
35
100%
|
32
100%
|
34
100%
|
118
100%
|
| Transgender spectrum |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| HIV-1 Infection Status (Count of Participants) | |||||
| HIV-1 infection present |
17
100%
|
35
100%
|
32
100%
|
0
0%
|
84
71.2%
|
| HIV-1 infection absent |
0
0%
|
0
0%
|
0
0%
|
34
100%
|
34
28.8%
|
Outcome Measures
| Title | LNG Area Under the Concentration-time Curve (AUC0-8h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants |
|---|---|
| Description | AUC for each participant was calculated from all available LNG concentrations measured over 8 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification (LLOQ) for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose). |
| Time Frame | Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame. |
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Measure Participants | 17 | 35 | 32 | 34 |
| Median (Inter-Quartile Range) [hours * ng/mL] |
52.13
|
102.13
|
80.50
|
124.39
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Confidence Interval (CI) on Geometric Mean Ratio compared to reference interval (0.7, 1.43). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.99 | |
| Confidence Interval |
(2-Sided) 90% 0.81 to 1.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned), D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Confidence Interval on Geometric Mean Ratio compared to reference interval (0.7, 1.43). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.34 | |
| Confidence Interval |
(2-Sided) 90% 1.12 to 1.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Confidence Interval on Geometric Mean Ratio excluding 1. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.66 | |
| Confidence Interval |
(2-Sided) 90% 1.27 to 2.18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Confidence Interval on Geometric Mean Ratio excluding 1. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.59 | |
| Confidence Interval |
(2-Sided) 90% 0.45 to 0.78 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
| Title | Number and Percentage of Participants Experiencing Either a Serious Adverse Event (SAE) or Adverse Event (AE) Potentially or Definitely Associated With Single Dose LNG Administration. |
|---|---|
| Description | Adverse events were 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 and DAIDS AE Grading Table Addendum 1, Female Genital Grading Table for Use in Microbicide Studies, Version 1.0 - November 2007. Relationship of AE to study treatment was determined by the site, study core team, and DAIDS clinical representative. AEs evaluated in this outcome fulfilled the below criteria: Potentially or definitely related to LNG dose Grade 3 or higher AEs Grade 2 of higher nausea, diarrhea, menorrhagia or metrorrhagia, and ectopic pregnancies |
| Time Frame | From Day 0 through study Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received LNG study treatment, grouped by LNG dose. LNG 1.5mg includes Group A (LNG 1.5 mg Among Participants on EFV-based ART (Randomized)) and Group C (LNG 1.5 mg Among Participants on DTG-based ART (Assigned)) participants. LNG 3.0mg includes Group B (LNG 3.0 mg Among Participants on EFV-based ART (Randomized)) and Group D (LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned)) participants. |
| Arm/Group Title | LNG 1.5 mg | LNG 3.0 mg |
|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Measure Participants | 52 | 70 |
| Count of Participants [Participants] |
2
11.8%
|
2
5.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.00 |
| Comments | No adjustments for multiple comparisons were made. Statistical significance was declared if p<0.05. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Maximum Concentration (Cmax) of LNG |
|---|---|
| Description | Cmax for each participant was calculated as the maximum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmax using the software package Phoenix WinNonLin (Certara®). |
| Time Frame | Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame. |
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Measure Participants | 17 | 35 | 32 | 34 |
| Median (Inter-Quartile Range) [ng/mL] |
15.10
|
24.90
|
18.65
|
28.01
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.17 | |
| Confidence Interval |
(2-Sided) 90% 0.96 to 1.41 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned), D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.43 | |
| Confidence Interval |
(2-Sided) 90% 1.21 to 1.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.51 | |
| Confidence Interval |
(2-Sided) 90% 1.17 to 1.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.77 | |
| Confidence Interval |
(2-Sided) 90% 0.60 to 1.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
| Title | Minimum Concentration (Cmin) of LNG |
|---|---|
| Description | Cmin for each participant was calculated as the minimum observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Cmin using the software package Phoenix WinNonLin (Certara®). Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose). |
| Time Frame | Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame. |
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Measure Participants | 17 | 35 | 32 | 34 |
| Median (Inter-Quartile Range) [ng/mL] |
0.25
|
0.56
|
1.49
|
0.41
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.37 | |
| Confidence Interval |
(2-Sided) 90% 0.22 to 0.61 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned), D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.25 | |
| Confidence Interval |
(2-Sided) 90% 0.15 to 0.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 2.11 | |
| Confidence Interval |
(2-Sided) 90% 1.20 to 3.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.17 | |
| Confidence Interval |
(2-Sided) 90% 0.09 to 0.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
| Title | Oral Clearance (CL/F) of LNG |
|---|---|
| Description | Apparent oral clearance (CL/F) for each participant was calculated as CL/F = dose/AUC0-24 or CL/F = dose/AUC0-48 of the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine CL/F using the software package Phoenix WinNonLin (Certara®). |
| Time Frame | Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame. |
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Measure Participants | 17 | 35 | 32 | 34 |
| Median (Inter-Quartile Range) [L/h] |
12.64
|
15.24
|
4.39
|
12.05
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 4.03 | |
| Confidence Interval |
(2-Sided) 90% 3.17 to 5.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned), D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 2.92 | |
| Confidence Interval |
(2-Sided) 90% 2.33 to 3.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.11 | |
| Confidence Interval |
(2-Sided) 90% 0.82 to 1.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 3.62 | |
| Confidence Interval |
(2-Sided) 90% 2.65 to 4.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
| Title | Volume of Distribution (Vd) of LNG |
|---|---|
| Description | Vd for each participant was calculated from observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine Vd using the software package Phoenix WinNonLin (Certara®). |
| Time Frame | Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame. |
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Measure Participants | 17 | 35 | 32 | 34 |
| Median (Inter-Quartile Range) [L] |
276.70
|
294.92
|
169.05
|
156.31
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 2.10 | |
| Confidence Interval |
(2-Sided) 90% 1.66 to 2.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned), D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.11 | |
| Confidence Interval |
(2-Sided) 90% 0.89 to 1.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.20 | |
| Confidence Interval |
(2-Sided) 90% 0.87 to 1.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.75 | |
| Confidence Interval |
(2-Sided) 90% 1.24 to 2.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
| Title | Half-life (T1/2) of LNG |
|---|---|
| Description | T1/2 for each participant was calculated using regression analysis when possible from the observed LNG concentration from LNG PK samples at pre-dose through 48 hours post-dose. Standard noncompartmental techniques were used to determine T1/2 using the software package Phoenix WinNonLin (Certara®). |
| Time Frame | Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame. |
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Measure Participants | 17 | 35 | 32 | 34 |
| Median (Inter-Quartile Range) [hours] |
12.05
|
11.79
|
24.03
|
8.97
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.52 | |
| Confidence Interval |
(2-Sided) 90% 0.46 to 0.59 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned), D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.38 | |
| Confidence Interval |
(2-Sided) 90% 0.34 to 0.43 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.08 | |
| Confidence Interval |
(2-Sided) 90% 0.93 to 1.25 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.48 | |
| Confidence Interval |
(2-Sided) 90% 0.41 to 0.56 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
| Title | Time of Minimum Concentration (Tmin) of LNG |
|---|---|
| Description | Tmin for each participant was time to the minimum observed LNG concentration after the observed dose. |
| Time Frame | Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame. |
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Measure Participants | 17 | 35 | 32 | 34 |
| Median (Inter-Quartile Range) [hours] |
47.07
|
47.95
|
47.61
|
48.00
|
| Title | LNG Area Under the Concentration Time Curve (AUC0-24h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants |
|---|---|
| Description | AUC for each participant was calculated from all available LNG concentrations measured over 24 hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose). |
| Time Frame | Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame. |
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Measure Participants | 17 | 35 | 32 | 34 |
| Median (Inter-Quartile Range) [hours * ng/mL] |
81.64
|
153.40
|
157.56
|
213.69
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.75 | |
| Confidence Interval |
(2-Sided) 90% 0.60 to 0.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned), D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.10 | |
| Confidence Interval |
(2-Sided) 90% 0.90 to 1.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.74 | |
| Confidence Interval |
(2-Sided) 90% 1.29 to 2.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.43 | |
| Confidence Interval |
(2-Sided) 90% 0.32 to 0.58 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
| Title | LNG Area Under the Concentration Time Curve (AUC0-48h) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants |
|---|---|
| Description | AUC for each participant was calculated from all available LNG concentrations measured over 48 hours using the linear up/log down version of the trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose). |
| Time Frame | Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame. |
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Measure Participants | 17 | 35 | 32 | 34 |
| Median (Inter-Quartile Range) [hours * ng/mL] |
98.95
|
180.25
|
224.81
|
242.68
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.62 | |
| Confidence Interval |
(2-Sided) 90% 0.49 to 0.78 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned), D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.89 | |
| Confidence Interval |
(2-Sided) 90% 0.71 to 1.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.77 | |
| Confidence Interval |
(2-Sided) 90% 1.31 to 2.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.35 | |
| Confidence Interval |
(2-Sided) 90% 0.26 to 0.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
| Title | LNG Total Area Under the Concentration Time Curve AUCinf (Infinity) Calculated Based on Intensive LNG PK Samples Obtained From Individual Participants |
|---|---|
| Description | AUC for each participant was calculated from all available LNG concentrations measured to infinity hours using the linear up/log down version of trapezoidal rule (i.e., noncompartmental technique) using the software package Phoenix WinNonLin (Certara®). This version of the trapezoidal rule used linear interpolation between untransformed data up to Cmax, and between log-transformed data from Cmax through Clast. Assay lower limit of quantification for LNG was 0.025 ng/mL; values < LLOQ were imputed as 0 (if pre-dose) or as 0.0125 (if post-dose). |
| Time Frame | Intensive LNG PK samples at pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, and 48 hours pose-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who took assigned dose of LNG and prescribed doses of background drugs (ART or TB treatment) and who had LNG PK concentrations available over the sampling time frame. |
| Arm/Group Title | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. |
| Measure Participants | 17 | 35 | 32 | 34 |
| Median (Inter-Quartile Range) [hours * ng/mL] |
118.71
|
196.83
|
345.80
|
248.96
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.50 | |
| Confidence Interval |
(2-Sided) 90% 0.39 to 0.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned), D: LNG 3.0 mg Among Participants on RIF-INH TB Therapy (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.69 | |
| Confidence Interval |
(2-Sided) 90% 0.55 to 0.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group D / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), B: LNG 3.0 mg Among Participants on EFV-based ART (Randomized) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.80 | |
| Confidence Interval |
(2-Sided) 90% 1.32 to 2.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group B / group A) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | A: LNG 1.5 mg Among Participants on EFV-based ART (Randomized), C: LNG 1.5 mg Among Participants on DTG-based ART (Assigned) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | No hypothesis testing was performed. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.28 | |
| Confidence Interval |
(2-Sided) 90% 0.20 to 0.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The ratios of the geometric means (group A / group C) and its 90% CI were obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data. | |
Adverse Events
| Time Frame | From study entry to study completion at Day 28 or premature study discontinuation. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The DAIDS AE Grading Table (V2.1) and Addendum 1, Female Genital Grading Table for Use in Microbicide Studies, Version 1.0 - November 2007 were used. AEs were recorded on the case report forms (CRFs) if any of the following criteria had been met: All Grade ≥3 AEs considered potentially or definitely related to LNG All Grade ≥2 nausea, diarrhea, menorrhagia, or metrorrhagia Ectopic pregnancy All AEs meeting Serious Adverse Event (SAE) definition | |||||||
| Arm/Group Title | A: LNG 1.5 mg Among Women on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Women on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Women on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Women on RIF-INH TB Therapy (Assigned) | ||||
| Arm/Group Description | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 1.5 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | Participants received 3 mg of LNG once orally on Day 0 and were followed post-treatment for 4 weeks. | ||||
All Cause Mortality |
||||||||
| A: LNG 1.5 mg Among Women on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Women on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Women on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Women on RIF-INH TB Therapy (Assigned) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | 0/36 (0%) | 0/35 (0%) | 0/34 (0%) | ||||
Serious Adverse Events |
||||||||
| A: LNG 1.5 mg Among Women on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Women on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Women on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Women on RIF-INH TB Therapy (Assigned) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | 0/36 (0%) | 0/35 (0%) | 1/34 (2.9%) | ||||
| Nervous system disorders | ||||||||
| Epilepsy | 0/17 (0%) | 0/36 (0%) | 0/35 (0%) | 1/34 (2.9%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| A: LNG 1.5 mg Among Women on EFV-based ART (Randomized) | B: LNG 3.0 mg Among Women on EFV-based ART (Randomized) | C: LNG 1.5 mg Among Women on DTG-based ART (Assigned) | D: LNG 3.0 mg Among Women on RIF-INH TB Therapy (Assigned) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/17 (5.9%) | 0/36 (0%) | 1/35 (2.9%) | 3/34 (8.8%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/17 (0%) | 0/36 (0%) | 0/35 (0%) | 1/34 (2.9%) | ||||
| Abdominal pain lower | 0/17 (0%) | 0/36 (0%) | 0/35 (0%) | 1/34 (2.9%) | ||||
| Nausea | 0/17 (0%) | 0/36 (0%) | 1/35 (2.9%) | 2/34 (5.9%) | ||||
| Nervous system disorders | ||||||||
| Headache | 0/17 (0%) | 0/36 (0%) | 0/35 (0%) | 1/34 (2.9%) | ||||
| Reproductive system and breast disorders | ||||||||
| Heavy menstrual bleeding | 1/17 (5.9%) | 0/36 (0%) | 0/35 (0%) | 1/34 (2.9%) | ||||
| Intermenstrual bleeding | 0/17 (0%) | 0/36 (0%) | 0/35 (0%) | 1/34 (2.9%) | ||||
| Menstrual discomfort | 0/17 (0%) | 0/36 (0%) | 0/35 (0%) | 1/34 (2.9%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
| Name/Title | ACTG Clinicaltrials.gov Coordinator |
|---|---|
| Organization | ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company. |
| Phone | (301) 628-3348 |
| ACTGCT.gov@fstrf.org |
- ACTG A5375
- 38493
- UM1AI068636