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Evaluating Pharmacokinetic Interactions With Vaginal Ring Contraceptives and ART

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ClinicalTrials.gov Identifier: NCT01903031
Recruitment Status : Completed
First Posted : July 19, 2013
Results First Posted : January 4, 2018
Last Update Posted : June 6, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: HIV-1 Infection
Interventions: Device: Nuvaring
Drug: EFV
Drug: ATV/r
Drug: TDF
Drug: NRTIs

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The first participant enrolled in December 2014 and final participant enrolled in September 2016. Enrollment took place at 21 US and non-US clinical research sites.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
NuvaRing and no ART Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
NuvaRing With EFV Plus ≥2 NRTIs NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.

Participant Flow:   Overall Study
    NuvaRing and no ART   NuvaRing With EFV Plus ≥2 NRTIs   NuvaRing With ATV/r Plus TDF and ≥1 NRTIs
STARTED   27   28   29 
COMPLETED   25   25   24 
NOT COMPLETED   2   3   5 
Not Able to Attend Clinic                1                1                0 
Missed Day 21 Primary Endpoint Visit                1                0                0 
Adverse Event                0                1                0 
Withdrawal by Subject                0                1                1 
Protocol Violation                0                0                2 
Lost to Follow-up                0                0                1 
NuvaRing removed prior to Day 21 visit                0                0                1 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants enrolled.

Reporting Groups
  Description
NuvaRing and no ART Participants who were not on ART were prescribed NuvaRing, to be inserted at entry and removed at Day 21.
NuvaRing With EFV Plus ≥2 NRTIs NuvaRing was inserted at entry and removed at Day 21. Participants also received EFV 600 mg daily with two or more NRTIs.
NuvaRing With ATV/r Plus TDF and ≥1 NRTIs NuvaRing was inserted at entry and removed at Day 21. Participants also received ATV/r 300 mg/ 100 mg daily with tenofovir (TDF) 300 mg and 1 or more additional NRTIs.
Total Total of all reporting groups

Baseline Measures
   NuvaRing and no ART   NuvaRing With EFV Plus ≥2 NRTIs   NuvaRing With ATV/r Plus TDF and ≥1 NRTIs   Total 
Overall Participants Analyzed 
[Units: Participants]
 27   28   29   84 
Age 
[Units: Years]
Median (Full Range)
 32 
 (22 to 48) 
 36 
 (17 to 55) 
 36 
 (22 to 50) 
 35 
 (17 to 55) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female   27   28   29   84 
Male   0   0   0   0 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
       
White Non-Hispanic      1   3.7%      1   3.6%      1   3.4%      3   3.6% 
Black Non-Hispanic      12  44.4%      18  64.3%      14  48.3%      44  52.4% 
Hispanic (Regardless of Race)      11  40.7%      9  32.1%      9  31.0%      29  34.5% 
Asian, Pacific Islander      3  11.1%      0   0.0%      5  17.2%      8   9.5% 
Region of Enrollment 
[Units: Participants]
Count of Participants
       
Puerto Rico   1   0   2   3 
United States   5   14   15   34 
Botswana   4   1   0   5 
Brazil   3   6   5   14 
South Africa   2   0   0   2 
Kenya   3   3   2   8 
Thailand   3   0   5   8 
Peru   6   4   0   10 


  Outcome Measures

1.  Primary:   Etonogestrel Concentrations at Study Day 21   [ Time Frame: Day 21 ]

2.  Primary:   Ethinyl Estradiol Concentrations at Study Day 21   [ Time Frame: Day 21 ]

3.  Secondary:   Etonogestrel Concentrations Obtained on Study Days 7 and 14   [ Time Frame: Study days 7 and 14 ]

4.  Secondary:   Ethinyl Estradiol Concentrations Obtained on Study Days 7 and 14.   [ Time Frame: Study days 7 and 14 ]

5.  Secondary:   EFV PK Parameter Area Under the Concentration-Time Curve (AUC0-24hours) Calculated Based on Intensive EFV PK Samples Obtained From Individual Participants Enrolled in Arm B   [ Time Frame: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement). ]

6.  Secondary:   EFV PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B   [ Time Frame: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement). ]

7.  Secondary:   EFV PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B   [ Time Frame: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement). ]

8.  Secondary:   EFV PK Parameter Clearance (CLss/F) Determined Based on EFV Levels From Individual Participants Enrolled in Arm B   [ Time Frame: Intensive EFV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement). ]

9.  Secondary:   ATV PK Parameter AUC(0-24h) Calculated Based on Intensive Atazanavir (ATV) PK Samples Obtained From Individual Participants Enrolled in Arm C   [ Time Frame: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement) ]

10.  Secondary:   ATV PK Parameter Cmin Determined Based on ATV Levels From Individual Participants Enrolled in Arm C   [ Time Frame: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement). ]

11.  Secondary:   ATV PK Parameter Cmax Determined Based on ATV Levels From Individual Participants Enrolled in Arm C   [ Time Frame: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement). ]

12.  Secondary:   ATV PK Parameter Time to Cmax (Tmax) Determined Based on ATV Levels From Individual Participants Enrolled in Arm C   [ Time Frame: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement). ]

13.  Secondary:   ATV PK Parameter CLss/F Determined Based on ATV Levels From Individual Participants Enrolled in Arm C   [ Time Frame: Intensive ATV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement). ]

14.  Secondary:   Ritonavir (RTV) PK Parameter AUC(0-24h) Calculated Based on Intensive RTV PK Samples Obtained From Individual Participants Enrolled in Arm C   [ Time Frame: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement) ]

15.  Secondary:   RTV PK Parameter Cmin Determined Based on RTV Levels From Individual Participants Enrolled in Arm C   [ Time Frame: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement) ]

16.  Secondary:   RTV PK Parameter Cmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C   [ Time Frame: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement) ]

17.  Secondary:   RTV PK Parameter Tmax Determined Based on RTV Levels From Individual Participants Enrolled in Arm C   [ Time Frame: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement) ]

18.  Secondary:   RTV PK Parameter CLss/F Determined Based on RTV Levels From Individual Participants Enrolled in Arm C   [ Time Frame: Intensive RTV PK samples at pre-dose, 1, 3, 4, 5, and 8 hours post-dose on study day 0 (before vaginal ring placement) and on study day 21 (3 weeks after vaginal ring placement) ]

19.  Secondary:   Proportion of Participants With Plasma HIV-1 RNA Levels <40 Copies/mL   [ Time Frame: Study day 0 and study day 21 ]

20.  Secondary:   Percentage of Participants With Signs and Symptoms of Grade 2 or Higher Deemed Possibly, Probably or Definitely Related to Study Treatment   [ Time Frame: From day 0 to day 28 ]

21.  Secondary:   Proportion of Participants With Progesterone Levels Greater Than 5 ng/mL.   [ Time Frame: Study days 0, 7, 14, 21 and 28 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
phone: (301) 628-3313
e-mail: ACTGCT.Gov@s-3.com



Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01903031     History of Changes
Other Study ID Numbers: ACTG A5316
UM1AI068636 ( U.S. NIH Grant/Contract )
First Submitted: July 16, 2013
First Posted: July 19, 2013
Results First Submitted: December 1, 2017
Results First Posted: January 4, 2018
Last Update Posted: June 6, 2018