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CompletedNCT02817464Updated Feb 12, 2024Results posted

Study to Evaluate Suppression of Ovulation and Pharmacokinetics of Medroxyprogesterone Acetate Following Administration of TV-46046 in Women With Ovulatory Cycle

A Phase 1 interventional study of TV-46046 - 400 mg/mL and TV-46046 - 200 mg/mL in Pregnancy and Contraception, sponsored by Teva Branded Pharmaceutical Products R&D, Inc.. Completed at 2 sites in United States. Open to female participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-02-12.

Sponsored by Teva Branded Pharmaceutical Products R&D, Inc. · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
12
Allocation
Randomized
Ages
18 Years to 40 Years
Sex
Female
01

Study summary

The purpose of this pharmacodynamic and pharmacokinetic study is to identify a dose of TV-46046 (within the range 80 to 300 mg) that is both safe and consistent with contraceptive effect when injected every 6 months.

02

Conditions studied

  • Pregnancy
  • Contraception
03

In context

Lead sponsor

Teva Branded Pharmaceutical Products R&D, Inc. is the lead sponsor of 205 studies on the registry; none are open to participants now.

Of its 49 completed or terminated interventional studies of FDA-regulated products, 47 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 40 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  • has regular menstrual cycle (24 to 35 days)
  • is at low risk of pregnancy (ie, sterilized, in exclusively same-sex partnership, in monogamous relationship with vasectomized partner, or using non-hormonal IUD)
  • is in good general health as determined by a medical history and physical examination
  • is not pregnant and does not have desire to become pregnant in the subsequent 36 months

  • has had a normal mammogram within the last year (for Part 1 only)

    • additional criteria apply, please contact the investigator for more information

Exclusion criteria

Exclusion Criteria:

  • has hypertension:

    • systolic blood pressure (BP) ≥160 mm Hg or diastolic BP ≥100 mm Hg
    • vascular disease
  • has current or history of ischemic heart disease
  • has history of stroke
  • has history of thromboembolic event

  • has systemic lupus erythematosus

    • positive (or unknown) antiphospholipid antibodies
    • severe thrombocytopenia
  • has rheumatoid arthritis on immunosuppressive therapy
  • has migraine with aura
  • has unexplained vaginal bleeding
  • has diabetes
  • has strong family history of breast cancer (defined as one or more first degree relatives, breast cancer occurring before menopause in three or more family members, regardless of degree of relationship, and any male family member with breast cancer), or current or history of breast cancer, or undiagnosed mass detected by breast exam
  • has current or history of cervical cancer
  • has severe cirrhosis (decompensated) or liver tumors
  • has known significant renal disease
  • used Depo-Provera Contraceptive Injection or Depo-subcutaneous Provera 104 (DMPA) products in the past 12 months

  • used any of the following medications within 1 month prior to enrollment:

    • any investigational drug
    • prohibited drugs per protocol
    • oral contraceptives, contraceptive ring or patch
    • levonorgestrel intrauterine system (LNG IUS) or contraceptive implant
  • used a combined injectable contraceptive in the past 6 months
  • less than 3 months since the end of last pregnancy
  • currently lactating
  • is using or plans to use prohibited drugs per protocol in the next 18 months
  • has known sensitivity to MPA or inactive ingredients
  • has a plan to move to another location in the next 24 months

  • in the opinion of the investigator, potentially at elevated risk of HIV infection (eg, HIV -positive partner, IV drug use by self or by partner)

    • additional criteria apply, please contact the investigator for more information
05

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Randomized
Intervention model
Single group
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
12 participants (actual)

Study arms

  • Experimental
    TV-46046 - 1

    Drug: TV-46046 - 400 mg/mL

  • Experimental
    TV-46046 - 2

    Drug: TV-46046 - 200 mg/mL

Interventions

  • DrugTV-46046 - 400 mg/mL

    A single subcutaneous injection in the abdomen of undiluted TV-46046 - 400 mg/mL

  • DrugTV-46046 - 200 mg/mL

    A single subcutaneous injection in the abdomen of saline-diluted TV-46046 - 200 mg/mL

06

What researchers measure

Primary outcomes

  1. Part 1: Serum Medroxyprogesterone Acetate (MPA) Concentration at Day 1

    'Overall number of participants analyzed' = participants evaluable for this outcome measure.

    Time frame: Day 1

  2. Part 1: Serum MPA Concentration at Day 7

    Time frame: Day 7

  3. Part 1: Serum MPA Concentration at Day 28

    Time frame: Day 28

  4. Part 1: Serum MPA Concentration at Day 91

    Time frame: Day 91

  5. Part 1: Serum MPA Concentration at Day 182

    Time frame: Day 182

  6. Part 1: Serum MPA Concentration at Day 210

    Time frame: Day 210

  7. Part 1: Maximum Observed Serum Concentration (Cmax) of MPA

    Time frame: Day 0 up to Week 52

  8. Part 1: Observed Serum Drug Concentration at Day 182 (C182) of MPA

    Time frame: Day 182

  9. Part 1: Time to Reach Cmax (Tmax) of MPA

    Time frame: Day 0 up to Week 52

  10. Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 182 (AUC0-182) of MPA

    Time frame: Day 0 up to Day 182

  11. Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 210 (AUC0-210) of MPA

    Time frame: Day 0 up to Day 210

  12. Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Infinity (AUC0-∞) of MPA

    Time frame: Day 0 up to Week 52

  13. Part 1: Apparent Terminal Half-life (t1/2) of MPA

    Time frame: Day 0 up to Week 52

  14. Part 2: Time to Ovulation

    Ovulation was defined as a single elevated serum progesterone ≥4.7 ng/mL.

    Time frame: Day 0 up to Week 78

Secondary outcomes

  1. Part 1: Time to Ovulation

    Ovulation was defined as a single elevated serum progesterone ≥4.7 ng/mL. Time to ovulation was computed as the difference in days between detection of the first post-randomization elevated progesterone and the date of treatment initiation. Median time to ovulation was derived using Kaplan-Meier estimate.

    Time frame: Day 0 up to Week 78

  2. Part 2: Cmax of MPA

    Time frame: Day 0 up to Week 52

  3. Part 2: Tmax of MPA

    Time frame: Day 0 up to Week 52

  4. Part 2: Observed Serum Drug Concentration at Day 210 (C210) of MPA

    Time frame: Day 0 up to Day 210

  5. Part 2: C182 of MPA

    Time frame: Day 0 up to Day 182

  6. Part 2: AUC0-182 of MPA

    Time frame: Day 0 up to Day 182

  7. Part 2: AUC0-210 of MPA

    Time frame: Day 0 up to Day 210

  8. Part 2: AUC0-∞ of MPA

    Time frame: Day 0 up to Week 52

  9. Part 2: Apparent Terminal Half Life (t1/2) of MPA

    Time frame: Day 0 up to Week 52

  10. Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

    Time frame: Day 0 up to Week 78

07

Results

Posted Feb 12, 2024
Limitations and caveats
This study was planned to be conducted in 2 parts (Part 1: Exploratory PK, and Part 2: Dose-range Finding). Due to suboptimal long-term stability and re-suspendability, the decision was made not to initiate Part 2 of this clinical study.

Participant flow

This was a 2-part study: Part 1 (Exploratory Pharmacokinetics \[PK\]) and Part 2 (Dose-range Finding).

Participant flow — Overall Study
MilestoneGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Started66
Received at least 1 dose of study drug66
Completed45
Not completed21
Withdrew: Lost to follow-up10
Withdrew: Discontinued early due to personal decision11

Outcome measures

PrimaryPart 1: Serum Medroxyprogesterone Acetate (MPA) Concentration at Day 1

'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Time frame:
Day 1
Reported as:
Mean · nanograms (ng)/milliliter (mL)
Part 1: Serum Medroxyprogesterone Acetate (MPA) Concentration at Day 1
nanograms (ng)/milliliter (mL)Group 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Serum Medroxyprogesterone Acetate (MPA) Concentration at Day 10.36 ± 0.130.67 ± 0.22
PrimaryPart 1: Serum MPA Concentration at Day 7
Time frame:
Day 7
Reported as:
Mean · ng/mL
Part 1: Serum MPA Concentration at Day 7
ng/mLGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Serum MPA Concentration at Day 70.37 ± 0.100.70 ± 0.22
PrimaryPart 1: Serum MPA Concentration at Day 28
Time frame:
Day 28
Reported as:
Mean · ng/mL
Part 1: Serum MPA Concentration at Day 28
ng/mLGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Serum MPA Concentration at Day 280.36 ± 0.070.69 ± 0.25
PrimaryPart 1: Serum MPA Concentration at Day 91
Time frame:
Day 91
Reported as:
Mean · ng/mL
Part 1: Serum MPA Concentration at Day 91
ng/mLGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Serum MPA Concentration at Day 910.41 ± 0.130.62 ± 0.09
PrimaryPart 1: Serum MPA Concentration at Day 182
Time frame:
Day 182
Reported as:
Mean · ng/mL
Part 1: Serum MPA Concentration at Day 182
ng/mLGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Serum MPA Concentration at Day 1820.22 ± 0.080.17 ± 0.10
PrimaryPart 1: Serum MPA Concentration at Day 210
Time frame:
Day 210
Reported as:
Mean · ng/mL
Part 1: Serum MPA Concentration at Day 210
ng/mLGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Serum MPA Concentration at Day 2100.20 ± 0.050.12 ± 0.09
PrimaryPart 1: Maximum Observed Serum Concentration (Cmax) of MPA
Time frame:
Day 0 up to Week 52
Reported as:
Geometric mean · ng/mL
Part 1: Maximum Observed Serum Concentration (Cmax) of MPA
ng/mLGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Maximum Observed Serum Concentration (Cmax) of MPA0.53 (0.43 to 0.64)0.97 (0.73 to 1.29)
Statistical analysis
  • Group 1 (TV-46046 - Undiluted) vs Group 2 (TV-46046 - Saline-diluted) · Geometric mean ratio: 1.84 · 90% CI 1.44 to 2.36
PrimaryPart 1: Observed Serum Drug Concentration at Day 182 (C182) of MPA
Time frame:
Day 182
Reported as:
Geometric mean · ng/mL
Part 1: Observed Serum Drug Concentration at Day 182 (C182) of MPA
ng/mLGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Observed Serum Drug Concentration at Day 182 (C182) of MPA0.21 (0.14 to 0.31)0.14 (0.05 to 0.40)
Statistical analysis
  • Group 1 (TV-46046 - Undiluted) vs Group 2 (TV-46046 - Saline-diluted) · Geometric mean ratio: 0.66 · 90% CI 0.33 to 1.33
PrimaryPart 1: Time to Reach Cmax (Tmax) of MPA
Time frame:
Day 0 up to Week 52
Reported as:
Median · days
Part 1: Time to Reach Cmax (Tmax) of MPA
daysGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Time to Reach Cmax (Tmax) of MPA9.49 (1.96 to 40.96)47.99 (7.10 to 84.01)
PrimaryPart 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 182 (AUC0-182) of MPA
Time frame:
Day 0 up to Day 182
Reported as:
Geometric mean · days*ng/mL
Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 182 (AUC0-182) of MPA
days*ng/mLGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 182 (AUC0-182) of MPA58.61 (44.75 to 76.76)97.72 (82.20 to 116.18)
Statistical analysis
  • Group 1 (TV-46046 - Undiluted) vs Group 2 (TV-46046 - Saline-diluted) · Geometric mean ratio: 1.67 · 90% CI 1.33 to 2.09
PrimaryPart 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 210 (AUC0-210) of MPA
Time frame:
Day 0 up to Day 210
Reported as:
Geometric mean · days*ng/mL
Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 210 (AUC0-210) of MPA
days*ng/mLGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Day 210 (AUC0-210) of MPA63.91 (48.78 to 83.74)103.11 (88.40 to 120.27)
Statistical analysis
  • Group 1 (TV-46046 - Undiluted) vs Group 2 (TV-46046 - Saline-diluted) · Geometric mean ratio: 1.61 · 90% CI 1.30 to 2.01
PrimaryPart 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Infinity (AUC0-∞) of MPA
Time frame:
Day 0 up to Week 52
Reported as:
Geometric mean · days*ng/mL
Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Infinity (AUC0-∞) of MPA
days*ng/mLGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Area Under the Serum Drug Concentration by Time Curve From Time 0 to Infinity (AUC0-∞) of MPA94.56 (81.16 to 110.16)114.13 (98.77 to 131.88)
Statistical analysis
  • Group 1 (TV-46046 - Undiluted) vs Group 2 (TV-46046 - Saline-diluted) · Geometric mean ratio: 1.21 · 90% CI 1.04 to 1.40
PrimaryPart 1: Apparent Terminal Half-life (t1/2) of MPA
Time frame:
Day 0 up to Week 52
Reported as:
Geometric mean · days
Part 1: Apparent Terminal Half-life (t1/2) of MPA
daysGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Apparent Terminal Half-life (t1/2) of MPA82.87 (32.12 to 213.80)42.34 (23.20 to 77.28)
Statistical analysis
  • Group 1 (TV-46046 - Undiluted) vs Group 2 (TV-46046 - Saline-diluted) · Geometric mean ratio: 0.51 · 90% CI 0.23 to 1.13
PrimaryPart 2: Time to Ovulation

Ovulation was defined as a single elevated serum progesterone ≥4.7 ng/mL.

Time frame:
Day 0 up to Week 78

No measurements were reported for this outcome.

SecondaryPart 1: Time to Ovulation

Ovulation was defined as a single elevated serum progesterone ≥4.7 ng/mL. Time to ovulation was computed as the difference in days between detection of the first post-randomization elevated progesterone and the date of treatment initiation. Median time to ovulation was derived using Kaplan-Meier estimate.

Time frame:
Day 0 up to Week 78
Reported as:
Median · days
Part 1: Time to Ovulation
daysGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Part 1: Time to Ovulation328 (279 to 434)251 (196 to 291)
Statistical analysis
  • Group 1 (TV-46046 - Undiluted) vs Group 2 (TV-46046 - Saline-diluted) · Log Rank · p = 0.0073
SecondaryPart 2: Cmax of MPA
Time frame:
Day 0 up to Week 52

No measurements were reported for this outcome.

SecondaryPart 2: Tmax of MPA
Time frame:
Day 0 up to Week 52

No measurements were reported for this outcome.

SecondaryPart 2: Observed Serum Drug Concentration at Day 210 (C210) of MPA
Time frame:
Day 0 up to Day 210

No measurements were reported for this outcome.

SecondaryPart 2: C182 of MPA
Time frame:
Day 0 up to Day 182

No measurements were reported for this outcome.

SecondaryPart 2: AUC0-182 of MPA
Time frame:
Day 0 up to Day 182

No measurements were reported for this outcome.

SecondaryPart 2: AUC0-210 of MPA
Time frame:
Day 0 up to Day 210

No measurements were reported for this outcome.

SecondaryPart 2: AUC0-∞ of MPA
Time frame:
Day 0 up to Week 52

No measurements were reported for this outcome.

SecondaryPart 2: Apparent Terminal Half Life (t1/2) of MPA
Time frame:
Day 0 up to Week 52

No measurements were reported for this outcome.

SecondaryNumber of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame:
Day 0 up to Week 78
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
ParticipantsGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)66

Adverse events

Collected over Day 0 up to Week 78. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Group 1 (TV-46046 - Undiluted)0/6 (0%)0/6 (0%)6/6 (100%)
Group 2 (TV-46046 - Saline-diluted)0/6 (0%)1/6 (16.7%)6/6 (100%)
Most frequent serious events
Most frequent serious events
EventGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Suicide attemptPsychiatric disorders0/61/6
Most frequent other events
Showing 10 of 30
Most frequent other events
EventGroup 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)
Injection site reactionGeneral disorders5/64/6
Bacterial vaginosisInfections and infestations2/60/6
Viral upper respiratory tract infectionInfections and infestations2/62/6
RashSkin and subcutaneous tissue disorders0/62/6
Abdominal painGastrointestinal disorders0/61/6
Chest painGeneral disorders1/60/6
PyrexiaGeneral disorders1/60/6
ThirstGeneral disorders0/61/6
HypersensitivityImmune system disorders1/60/6
UrticariaImmune system disorders0/61/6

Baseline characteristics

Treated population included all screened participants who were enrolled and received a dose of study drug.

Age, Continuous
Age, Continuous(years)Group 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)Total
Mean29.5 ± 4.0434.2 ± 5.0831.8 ± 5.01
Sex: Female, Male
Sex: Female, Male(Participants)Group 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)Total
Female6612
Male000
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Group 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)Total
Hispanic or Latino202
Not Hispanic or Latino4610
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Group 1 (TV-46046 - Undiluted)Group 2 (TV-46046 - Saline-diluted)Total
American Indian or Alaska Native000
Asian101
Native Hawaiian or Other Pacific Islander000
Black or African American055
White516
More than one race000
Unknown or Not Reported000
08

Study locations

2 sites
  • Teva Investigational Site 001
    Philadelphia, Pennsylvania 19104, United States
  • Teva Investigational Site 002
    Norfolk, Virginia 23507, United States
09

References and documents

Study documents

  • Study protocol · Aug 9, 2017
  • Statistical analysis plan · Sep 26, 2018

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 12, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02817464
Lead sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Collaborators
FHI 360
Responsible party
Sponsor
First posted
Jun 29, 2016
Start date
Oct 26, 2016
Primary completion
Dec 3, 2018
Completion
Dec 3, 2018
Results posted
Feb 12, 2024
Last update
Feb 12, 2024

Study contacts

Teva Medical Expert, MD
study director · Teva Branded Pharmaceutical Products R&D, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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