Trial Outcomes & Findings for A Multicenter Study to Evaluate the Efficacy of a 91-Day Extended Cycle Oral Contraceptive for Menstrually-Related Migraine Headaches (NCT NCT00781456)
NCT ID: NCT00781456
Last Updated: 2017-02-06
Results Overview
The number of participants with at least 50% reduction in migraine frequency (average weekly number of migraine episodes) through the end of the 91-day treatment period compared with Baseline (the 25- to 35-day baseline qualification period). Participants recorded the incidence, timing and intensity of migraines in a migraine diary during the prequalification period and throughout the 91-day treatment period.
COMPLETED
PHASE2
109 participants
Baseline (25-35 days before Day 1) and Days 1-91
2017-02-06
Participant Flow
A total of 304 women with menstrually related migraine were screened for enrollment at 37 study centers in the United States. Of the 304 screened, 109 women at 23 centers met entry criteria and were considered eligible for enrollment into the study.
Participant milestones
| Measure |
91-day Levonorgestrel Oral Contraceptive
Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks.
|
Placebo
Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
58
|
51
|
|
Overall Study
Received Study Drug
|
57
|
49
|
|
Overall Study
COMPLETED
|
37
|
35
|
|
Overall Study
NOT COMPLETED
|
21
|
16
|
Reasons for withdrawal
| Measure |
91-day Levonorgestrel Oral Contraceptive
Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks.
|
Placebo
Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
3
|
|
Overall Study
Withdrawal by Subject
|
3
|
5
|
|
Overall Study
Protocol Violation
|
4
|
1
|
|
Overall Study
Noncompliance With Protocol
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
10
|
5
|
|
Overall Study
Other Reason, Unknown
|
0
|
1
|
Baseline Characteristics
A Multicenter Study to Evaluate the Efficacy of a 91-Day Extended Cycle Oral Contraceptive for Menstrually-Related Migraine Headaches
Baseline characteristics by cohort
| Measure |
91-day Levonorgestrel Oral Contraceptive
n=54 Participants
Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks.
|
Placebo
n=45 Participants
Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks.
|
Total
n=99 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
26.7 years
STANDARD_DEVIATION 4.70 • n=93 Participants
|
27.4 years
STANDARD_DEVIATION 3.83 • n=4 Participants
|
27.1 years
STANDARD_DEVIATION 4.32 • n=27 Participants
|
|
Gender
Female
|
54 Participants
n=93 Participants
|
45 Participants
n=4 Participants
|
99 Participants
n=27 Participants
|
|
Gender
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
28 participants
n=93 Participants
|
23 participants
n=4 Participants
|
51 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Black
|
11 participants
n=93 Participants
|
9 participants
n=4 Participants
|
20 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
2 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
14 participants
n=93 Participants
|
10 participants
n=4 Participants
|
24 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 participants
n=93 Participants
|
2 participants
n=4 Participants
|
2 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline (25-35 days before Day 1) and Days 1-91Population: Intent-to-treat population
The number of participants with at least 50% reduction in migraine frequency (average weekly number of migraine episodes) through the end of the 91-day treatment period compared with Baseline (the 25- to 35-day baseline qualification period). Participants recorded the incidence, timing and intensity of migraines in a migraine diary during the prequalification period and throughout the 91-day treatment period.
Outcome measures
| Measure |
91-day Levonorgestrel Oral Contraceptive
n=54 Participants
Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks.
|
Placebo
n=45 Participants
Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks.
|
|---|---|---|
|
Percentage of Participants With ≥ 50% Reduction in Migraine Frequency During the Treatment Period
|
48.1 percentage of participants
|
48.9 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Month1, Month 2 and Month 3Population: Intent-to-treat population with available data. N indicates the number of participants with available data at each time point.
The percentage of participants with at least 50% reduction in migraine frequency (average weekly number of migraine episodes) compared to Baseline at each month of the treatment period.
Outcome measures
| Measure |
91-day Levonorgestrel Oral Contraceptive
n=54 Participants
Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks.
|
Placebo
n=45 Participants
Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks.
|
|---|---|---|
|
Percentage of Participants With ≥ 50% Reduction in Migraine Frequency During the First, Second and Third Months
First Month (N=54, 45)
|
42.6 percentage of participants
|
37.8 percentage of participants
|
|
Percentage of Participants With ≥ 50% Reduction in Migraine Frequency During the First, Second and Third Months
Second Month (N=51, 44)
|
62.7 percentage of participants
|
52.3 percentage of participants
|
|
Percentage of Participants With ≥ 50% Reduction in Migraine Frequency During the First, Second and Third Months
Third Month (N=40, 37)
|
60.0 percentage of participants
|
64.9 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Month 1, Month 2 and Month 3Population: Intent-to-treat population with available data. N indicates the number of participants with available data at each time period.
Migraine severity was recorded by participants in the Baseline qualification diary and study migraine diary during the treatment period. Participants could report a severity of none (score = 0), mild (1), moderate (2), or severe (3). In general, if a headache was mild, daily activities could be resumed and little to no medication was taken. Moderate headaches required medication and effected daily activities. Severe headaches were debilitating and required medication. Average migraine severity is defined as the sum of the severity ratings divided by the total number of migraine episodes reported during the observation period (for example, Baseline, First Month, Second Month, Third Month, and 91-Day Treatment Period). A negative change from Baseline score indicates improvement in severity.
Outcome measures
| Measure |
91-day Levonorgestrel Oral Contraceptive
n=54 Participants
Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks.
|
Placebo
n=45 Participants
Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks.
|
|---|---|---|
|
Change From Baseline in Average Migraine Severity
91-Day Treatment Period (N=54, 45)
|
-0.37 units on a scale
Standard Error 0.097
|
-0.18 units on a scale
Standard Error 0.109
|
|
Change From Baseline in Average Migraine Severity
First Month (N=54, 45)
|
-0.55 units on a scale
Standard Error 0.138
|
-0.52 units on a scale
Standard Error 0.154
|
|
Change From Baseline in Average Migraine Severity
Second Month (N= 51, 44)
|
-0.98 units on a scale
Standard Error 0.158
|
-0.72 units on a scale
Standard Error 0.173
|
|
Change From Baseline in Average Migraine Severity
Third Month (N=40, 37)
|
-1.06 units on a scale
Standard Error 0.190
|
-0.66 units on a scale
Standard Error 0.197
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 2 and Month 3Population: Intent-to-treat population with available data. N indicates the number of participants with available data at each time period.
Participants recorded use of rescue medications for migraines in the migraine diary during the course of study treatment.
Outcome measures
| Measure |
91-day Levonorgestrel Oral Contraceptive
n=54 Participants
Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks.
|
Placebo
n=45 Participants
Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks.
|
|---|---|---|
|
Percentage of Participants Who Required Rescue Medications During the Study Period
Baseline (N=54, 45)
|
85.2 percentage of participants
|
75.6 percentage of participants
|
|
Percentage of Participants Who Required Rescue Medications During the Study Period
First Month (N=54, 45)
|
63.0 percentage of participants
|
55.6 percentage of participants
|
|
Percentage of Participants Who Required Rescue Medications During the Study Period
Second Month (N=51, 44)
|
45.1 percentage of participants
|
54.5 percentage of participants
|
|
Percentage of Participants Who Required Rescue Medications During the Study Period
Third Month (N=40, 37)
|
35.0 percentage of participants
|
62.2 percentage of participants
|
|
Percentage of Participants Who Required Rescue Medications During the Study Period
During the 91-day treatment period (N=54, 45)
|
72.2 percentage of participants
|
75.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Week 15Population: Intent-to-treat population with available data.
The migraine disability assessment (MIDAS) test is used to determine how severely migraines affect a patient's life. Participants were asked five questions about how often their headaches limited their ability to go to work or school, to do household work or to do family or leisure activities in the past 3 months. The MIDAS score equals the sum of the days answered for each question and ranges from 0 (no disability) to approximately 270 (severe disability; the upper bound is dependent on the number of days a participant would plan to work or participate in other activities). The MIDAS score is classified into four grades of severity: * 0 to 5: MIDAS Grade I, Little or no disability * 6 to 10: MIDAS Grade II, Mild disability * 11 to 20: MIDAS Grade III, Moderate disability * 21+: MIDAS Grade IV, Severe disability
Outcome measures
| Measure |
91-day Levonorgestrel Oral Contraceptive
n=46 Participants
Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks.
|
Placebo
n=40 Participants
Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks.
|
|---|---|---|
|
Change From Baseline in Migraine Disability Assessment
|
-7.8 units on a scale
Standard Deviation 16.26
|
-8.5 units on a scale
Standard Deviation 10.65
|
SECONDARY outcome
Timeframe: Baseline and Week 15Population: Analysis was not performed due to an error in the administration of the test.
The Headache Impact Test (HIT) is a tool used to measure the impact headaches have on patients' ability to function on the job, at school, at home and in social situations. HIT-6 consists of 6 questions each scored on a scale from Never (6 points) to Always (13 points). The total score ranges from 36 to 78 with higher scores indicating greater impact on life. There was an error in administration of the HIT-6 in this study. Question 6 was not administered, and question 3 from the MIDAS was included instead. Therefore, the total score of the HIT-6 could not be calculated.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 15 weeksPopulation: Safety population, consisting of all participants who received at least one dose of study drug.
An AE is any untoward medical occurrence in a clinical investigation participant and which does not necessarily have to have a causal relationship with this treatment or clinical study. The following definitions were used to assess AE severity: Mild: Awareness of signs or symptoms, but they are easily tolerated; Moderate: Enough discomfort to cause interference with usual activity; Severe: Incapacitating, with inability to perform usual activity. Relationship to study drug was assessed as either: None: Causal relationship can be ruled out; Possibly: Causal relationship at least reasonably possible, i.e. relationship cannot be ruled out; Definitely: Causal relationship is certain. A serious adverse event (SAE) is one that met any one of the following criteria: * Fatal or life threatening * Requires or prolongs in patient hospitalization * Results in persistent or significant disability/incapacity * Congenital anomaly / birth defect * Important medical event.
Outcome measures
| Measure |
91-day Levonorgestrel Oral Contraceptive
n=57 Participants
Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks.
|
Placebo
n=49 Participants
Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Any adverse event
|
32 participants
|
17 participants
|
|
Number of Participants With Adverse Events (AEs)
Mild adverse event
|
11 participants
|
2 participants
|
|
Number of Participants With Adverse Events (AEs)
Moderate adverse event
|
17 participants
|
10 participants
|
|
Number of Participants With Adverse Events (AEs)
Severe adverse event
|
4 participants
|
5 participants
|
|
Number of Participants With Adverse Events (AEs)
Adverse event not related to study drug
|
11 participants
|
6 participants
|
|
Number of Participants With Adverse Events (AEs)
Adverse event possibly related to study drug
|
20 participants
|
11 participants
|
|
Number of Participants With Adverse Events (AEs)
Adverse event related to study drug
|
1 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs)
Deaths
|
0 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs)
Other serious adverse event
|
0 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs)
Withdrawn due to adverse event
|
3 participants
|
3 participants
|
SECONDARY outcome
Timeframe: 91-day treatment periodPopulation: Safety population with available data
Bleeding and spotting were recorded by participants in the migraine diary during the 91-day treatment period.
Outcome measures
| Measure |
91-day Levonorgestrel Oral Contraceptive
n=56 Participants
Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks.
|
Placebo
n=47 Participants
Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks.
|
|---|---|---|
|
Mean Number of Days of Bleeding or Spotting
|
21.2 days
Standard Deviation 19.58
|
15.5 days
Standard Deviation 7.73
|
Adverse Events
91-day Levonorgestrel Oral Contraceptive
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
91-day Levonorgestrel Oral Contraceptive
n=57 participants at risk
Participants received 12 weeks (84 consecutive days) of active combination tablets containing 150 µg levonorgestrel (LNG)/30 µg ethinyl estradiol (EE), followed by 7 days of 10 µg EE monotherapy, for a total of 13 weeks.
|
Placebo
n=49 participants at risk
Participants received placebo, 12 weeks (84 consecutive days) of inactive tablets, followed by an additional 7 days of inactive tablets, for a total of 13 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
5.3%
3/57 • Number of events 4 • Up to 15 weeks
|
2.0%
1/49 • Number of events 1 • Up to 15 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
3.5%
2/57 • Number of events 2 • Up to 15 weeks
|
6.1%
3/49 • Number of events 3 • Up to 15 weeks
|
|
Gastrointestinal disorders
Nausea
|
19.3%
11/57 • Number of events 18 • Up to 15 weeks
|
6.1%
3/49 • Number of events 3 • Up to 15 weeks
|
|
Gastrointestinal disorders
Vomiting
|
7.0%
4/57 • Number of events 6 • Up to 15 weeks
|
4.1%
2/49 • Number of events 2 • Up to 15 weeks
|
|
Infections and infestations
Sinusitis
|
5.3%
3/57 • Number of events 3 • Up to 15 weeks
|
0.00%
0/49 • Up to 15 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
5.3%
3/57 • Number of events 4 • Up to 15 weeks
|
4.1%
2/49 • Number of events 2 • Up to 15 weeks
|
|
Reproductive system and breast disorders
Menorrhagia
|
8.8%
5/57 • Number of events 7 • Up to 15 weeks
|
4.1%
2/49 • Number of events 2 • Up to 15 weeks
|
|
Reproductive system and breast disorders
Metrorrhagia
|
10.5%
6/57 • Number of events 7 • Up to 15 weeks
|
6.1%
3/49 • Number of events 4 • Up to 15 weeks
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products, R&D Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
- Publication restrictions are in place
Restriction type: OTHER