Trial Outcomes & Findings for Study to Evaluate the Contraceptive Efficacy/Safety of a Low Dose EE/LNG Transdermal Contraceptive Delivery System (NCT NCT01181479)
NCT ID: NCT01181479
Last Updated: 2018-07-03
Results Overview
Pregnancy outcomes was determine by measuring Pearl index. Pearl Index is the number of on-therapy pregnancies times 1300 divided by the number of 28-day on-therapy cycles and is an estimate of the number of pregnancies per 100 woman-years of product use.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1504 participants
Primary outcome timeframe
AG200-15: 6 months; Lessina: 6 months; AG200-15: 1 year
Results posted on
2018-07-03
Participant Flow
Participant milestones
| Measure |
AG200-15 (Cycles 1-13)
Intervention with drug: AG200-15 containing ethinyl estradiol and levonorgestrel. Administered for cycles 1-13.
|
Lessina (Cycles 1-6)
The Lessina regimen was taken for Cycles 1-6.
|
Lessina (Cycles 1-6) Crossover to AG200-15 (Cycles 7-13)
Intervention with drug: Lessina containing 20 mcg ethinyl estradiol and 100 mcg levonorgestrel in 21 day regimen cycles 1-6 followed by AG200-15 for cycles 7-13.
|
|---|---|---|---|
|
Subjects Receive AG200-15 or Lessina
STARTED
|
1129
|
375
|
0
|
|
Subjects Receive AG200-15 or Lessina
COMPLETED
|
485
|
249
|
0
|
|
Subjects Receive AG200-15 or Lessina
NOT COMPLETED
|
644
|
126
|
0
|
|
Crossover Subjects Recieve AG200-15
STARTED
|
0
|
0
|
249
|
|
Crossover Subjects Recieve AG200-15
COMPLETED
|
0
|
0
|
150
|
|
Crossover Subjects Recieve AG200-15
NOT COMPLETED
|
0
|
0
|
99
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Evaluate the Contraceptive Efficacy/Safety of a Low Dose EE/LNG Transdermal Contraceptive Delivery System
Baseline characteristics by cohort
| Measure |
AG200-15
n=1043 Participants
Intervention is drug: AG200-15 containing ethinyl estradiol and levonorgestrel for cycles 1-13.
|
Lessina Crossover to AG200-15
n=230 Participants
Intervention with drug: Lessina containing 20 mcg ethinyl estradiol and 100 mcg levonorgestrel in 21 day regimen cycles 1-6 followed by AG200-15 for cycles 7-13.
|
Total
n=1273 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1038 Participants
n=5 Participants
|
228 Participants
n=7 Participants
|
1266 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
26.38 years
STANDARD_DEVIATION 5.663 • n=5 Participants
|
26.86 years
STANDARD_DEVIATION 5.738 • n=7 Participants
|
26.46 years
STANDARD_DEVIATION 5.677 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1043 Participants
n=5 Participants
|
230 Participants
n=7 Participants
|
1273 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
1043 participants
n=5 Participants
|
230 participants
n=7 Participants
|
1273 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: AG200-15: 6 months; Lessina: 6 months; AG200-15: 1 yearPopulation: Subjects in the Safety population, age 17-35 with a BMI \<32, were analyzed.
Pregnancy outcomes was determine by measuring Pearl index. Pearl Index is the number of on-therapy pregnancies times 1300 divided by the number of 28-day on-therapy cycles and is an estimate of the number of pregnancies per 100 woman-years of product use.
Outcome measures
| Measure |
AG200-15 for Cycle 7-13
n=675 Participants
Subjects that applied AG200-15 for cycles 7-13.
|
Lessina
n=220 Participants
Subjects that only received Lessina for cycles 1-6.
|
AG200-15 for Cycle 1-13
n=827 Participants
Subjects that applied AG200-15 for all cycles (1-13)
|
|---|---|---|---|
|
Pregnancy
|
5.41 Pearl Index
Interval 2.35 to 8.46
|
6.67 Pearl Index
Interval 0.84 to 12.5
|
6.43 Pearl Index
Interval 4.13 to 8.72
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsPopulation: Number of subjects with documented cycle information.
Measuring the breakthrough bleeding (BTB) and/or breakthrough spotting (BTS). Measured as a percent of total number of cycles in each Arm/Group with BTB and/or BTS.
Outcome measures
| Measure |
AG200-15 for Cycle 7-13
n=715 Participants
Subjects that applied AG200-15 for cycles 7-13.
|
Lessina
n=246 Participants
Subjects that only received Lessina for cycles 1-6.
|
AG200-15 for Cycle 1-13
Subjects that applied AG200-15 for all cycles (1-13)
|
|---|---|---|---|
|
Cycle Control
|
23.9 percentage of cycles with BTB/BTS
|
21.2 percentage of cycles with BTB/BTS
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Lessina: 6 months; AG200-15: 1 year; AG200-15: 6 monthsPopulation: Subjects that received contraceptive and were analyzed for LNG and EE.
Measurement of plasma concentrations of LNG and EE for cycles 2, 6 and 13.
Outcome measures
| Measure |
AG200-15 for Cycle 7-13
n=326 Participants
Subjects that applied AG200-15 for cycles 7-13.
|
Lessina
n=933 Participants
Subjects that only received Lessina for cycles 1-6.
|
AG200-15 for Cycle 1-13
n=144 Participants
Subjects that applied AG200-15 for all cycles (1-13)
|
|---|---|---|---|
|
Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE)
EE for cycle 2
|
35.4 pg/ml
Interval 31.9 to 38.8
|
30.5 pg/ml
Interval 29.0 to 32.1
|
NA pg/ml
Non-applicable because cycle 2 data entered here.
|
|
Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE)
EE cycle 6
|
40.1 pg/ml
Interval 33.3 to 46.9
|
36.7 pg/ml
Interval 34.3 to 39.0
|
NA pg/ml
Non-applicable because cycle 6 data entered here.
|
|
Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE)
EE cycle 13
|
NA pg/ml
Non-applicable because cycle 13 data entered here.
|
31 pg/ml
Interval 28.5 to 33.5
|
33.4 pg/ml
Interval 29.1 to 37.8
|
|
Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE)
LNG cycle 2
|
2386 pg/ml
Interval 2180.0 to 2592.0
|
1201 pg/ml
Interval 1136.0 to 1266.0
|
NA pg/ml
Non-applicable because cycle 2 data entered here.
|
|
Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE)
LNG cycle 6
|
2611 pg/ml
Interval 2355.0 to 2867.0
|
1753 pg/ml
Interval 1636.0 to 1871.0
|
NA pg/ml
Non-applicable because cycle 6 data entered here.
|
|
Pharmacokinetics of Levonorgestrel (LNG) and Ethinyl Estradiol (EE)
LNG cycle 13
|
NA pg/ml
Non-applicable because cycle 13 data entered here.
|
1590 pg/ml
Interval 1452.0 to 1727.0
|
1750 pg/ml
Interval 1521.0 to 1979.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 yearPopulation: Safety Population
Evaluation of irritation at application site was determined using the following scores: 0: None 1. Mild 2. Moderate 3. Severe
Outcome measures
| Measure |
AG200-15 for Cycle 7-13
n=1273 Participants
Subjects that applied AG200-15 for cycles 7-13.
|
Lessina
Subjects that only received Lessina for cycles 1-6.
|
AG200-15 for Cycle 1-13
Subjects that applied AG200-15 for all cycles (1-13)
|
|---|---|---|---|
|
Self-reported Irritation at Application Site
|
1.35 Score on scale
Standard Deviation 0.964
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 yearPopulation: Safety Population
Evaluation of patch adhesion was determined using the following scores: 0: \>= 90% adhered (no lift) 1. \>= 75% adhered but \< 90% (some edges showing lift) 2. \>= 50% adhered but \< 75% (half of system lifts off) 3. \< 50% (\> half of system lifts off, but undetached) 4. patch completely detached
Outcome measures
| Measure |
AG200-15 for Cycle 7-13
n=1273 Participants
Subjects that applied AG200-15 for cycles 7-13.
|
Lessina
Subjects that only received Lessina for cycles 1-6.
|
AG200-15 for Cycle 1-13
Subjects that applied AG200-15 for all cycles (1-13)
|
|---|---|---|---|
|
Patch Adhesion by Investigator Evaluation at Each Visit
|
0.29 Score on a scale
Standard Deviation 0.823
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 yearPopulation: Safety Population
Evaluation of itching at patch application site was determined using the following scores: 0: None 1. Mild 2. Moderate 3. Severe
Outcome measures
| Measure |
AG200-15 for Cycle 7-13
n=1273 Participants
Subjects that applied AG200-15 for cycles 7-13.
|
Lessina
Subjects that only received Lessina for cycles 1-6.
|
AG200-15 for Cycle 1-13
Subjects that applied AG200-15 for all cycles (1-13)
|
|---|---|---|---|
|
Self-reported Itching at Patch Application Site
|
1.48 Score on a scale
Standard Deviation 0.948
|
—
|
—
|
Adverse Events
All AG200-15
Serious events: 14 serious events
Other events: 484 other events
Deaths: 0 deaths
Lessina
Serious events: 4 serious events
Other events: 112 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
All AG200-15
n=1273 participants at risk
All subjects that received AG200-15, including subjects that switched from Lessina to AG200-15 for cycles 7-13.
|
Lessina
n=344 participants at risk
Subjects that only received Lessina for cycles 1-6.
|
|---|---|---|
|
Psychiatric disorders
Suicidal Ideation
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
|
Infections and infestations
Pneumonia
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/1273
|
0.29%
1/344 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/1273
|
0.29%
1/344 • Number of events 1
|
|
Vascular disorders
Embolism Venous
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.16%
2/1273 • Number of events 2
|
0.29%
1/344 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
|
Gastrointestinal disorders
Vomiting
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
|
Gastrointestinal disorders
Gastointerstinal motility disorder
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
|
Injury, poisoning and procedural complications
Appendicitis
|
0.16%
2/1273 • Number of events 2
|
0.00%
0/344
|
|
Renal and urinary disorders
Calculus urinary
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
|
Musculoskeletal and connective tissue disorders
Compartment syndrome
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
|
Hepatobiliary disorders
Liver disorder
|
0.00%
0/1273
|
0.29%
1/344 • Number of events 1
|
|
Injury, poisoning and procedural complications
Overdose
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
|
Immune system disorders
Anaphylactic shock
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
|
Gastrointestinal disorders
Gastroenteritis
|
0.08%
1/1273 • Number of events 1
|
0.00%
0/344
|
Other adverse events
| Measure |
All AG200-15
n=1273 participants at risk
All subjects that received AG200-15, including subjects that switched from Lessina to AG200-15 for cycles 7-13.
|
Lessina
n=344 participants at risk
Subjects that only received Lessina for cycles 1-6.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
5.8%
74/1273 • Number of events 74
|
3.5%
12/344 • Number of events 12
|
|
Infections and infestations
Sinusitis
|
3.5%
45/1273 • Number of events 45
|
2.6%
9/344 • Number of events 9
|
|
Infections and infestations
Upper respiratory tract infection
|
4.0%
51/1273 • Number of events 51
|
2.0%
7/344 • Number of events 7
|
|
Infections and infestations
Urinary tract infection
|
3.5%
44/1273 • Number of events 44
|
3.2%
11/344 • Number of events 11
|
|
Reproductive system and breast disorders
Cervical Dysplasia
|
6.3%
80/1273 • Number of events 80
|
4.9%
17/344 • Number of events 17
|
|
Gastrointestinal disorders
Nausea
|
4.6%
58/1273 • Number of events 58
|
4.1%
14/344 • Number of events 14
|
|
Investigations
Human papilloma virus test positive
|
3.1%
40/1273 • Number of events 40
|
2.0%
7/344 • Number of events 7
|
|
Nervous system disorders
Headache
|
3.9%
50/1273 • Number of events 50
|
4.7%
16/344 • Number of events 16
|
|
Gastrointestinal disorders
Vomiting
|
1.7%
22/1273 • Number of events 22
|
2.9%
10/344 • Number of events 10
|
|
Reproductive system and breast disorders
Dysmenorrhea
|
1.6%
20/1273 • Number of events 20
|
2.6%
9/344 • Number of events 9
|
Additional Information
Joseph Chiodo III, Senior Medical Director
Agile Therapeutics
Phone: 609-683-1880
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Approval by Agile Therapeutics, Inc. of any publication, including oral presentations and abstracts, utilizing data or any information from the ATI-CL12 study is required prior to publication submission.
- Publication restrictions are in place
Restriction type: OTHER