Phase 3
N=409
To Compare SH T00658ID Over Ortho Tri-Cyclen Lo (US/Canada)
Contraception
Bottom Line
View on ClinicalTrials.gov: NCT00754065 ↗Enrolled (actual)
409
Serious AEs
1.8%
Results posted
Aug 2012
Primary outcome: Primary: The Change in Average of the 3 Highest Visual Analog Scale (VAS) Values of the Hormone Withdrawal-associated Symptoms Pelvic Pain or Headache During Cycle Days 22 to 28 From Baseline to Cycle 6 — 43.05; 34.97 mm — p=0.0024
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027) (Drug); Ortho Tri Cyclen Lo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Bayer
- Primary completion
- May 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Change in Average of the 3 Highest Visual Analog Scale (VAS) Values of the Hormone Withdrawal-associated Symptoms Pelvic Pain or Headache During Cycle Days 22 to 28 From Baseline to Cycle 6 |
43.05; 34.97 | 0.0024 sig |
| SECONDARY The Change From Baseline to Cycle 6 in the Number of Ibuprofen Tablets Used as Rescue Medication |
-1.6; -3.0; -5.8; -4.6 | — |
| SECONDARY The Change From Baseline to Cycle 13 in the Number of Ibuprofen Tablets Used as Rescue Medication |
-2.3; -3.5; -5.3; -5.2 | — |
| SECONDARY Change From Baseline to Cycle 6 in the Number of Days With at Least Moderate Pain/Intensity of Other Hormone-related Symptoms During Cycle Days 22-28 |
-1.950; -1.425; -1.921; -1.830; -1.179; -1.131 | — |
| SECONDARY Change From Baseline to Cycle 13 in the Number of Days With at Least Moderate Pain/Intensity of Other Hormone-related Symptoms During Cycle Days 22-28 |
-1.909; -1.419; -2.091; -2.065; -0.959; -1.379 | — |
| SECONDARY Change From Baseline to Cycle 6 in the Number of Days With at Least Moderate Pain/Intensity of Individual Hormone-related Symptoms During Cycle Days 1-21 |
-1.077; -0.968; -0.399; -0.624; -0.531; -0.210 | — |
| SECONDARY Change From Baseline to Cycle 13 in the Number of Days With at Least Moderate Pain/Intensity of Individual Hormone-related Symptoms During Cycle Days 1-21 |
-1.121; -0.767; -0.274; -0.643; -0.492; -0.279 | — |
| SECONDARY Change From Baseline to Cycle 6 in the Number of Days With at Least Moderate Pain/Intensity of Individual Hormone-related Symptoms During the Hormone-free Interval Cycle Days 27 to 28 for EV/DNG and Cycle Days 22 to 28 for EE/NGM |
-0.424; -1.425; -0.273; -1.830; -0.137; -1.131 | — |
| SECONDARY Change From Baseline to Cycle 13 in the Number of Days With at Least Moderate Pain/Intensity of Individual Hormone-related Symptoms During the Hormone-free Interval Cycle Days 27 to 28 for EV/DNG and Cycle Days 22 to 28 for EE/NGM |
-0.537; -1.419; -0.322; -2.065; -0.107; -1.379 | — |
| SECONDARY Change From Baseline to Cycle 3 in the Average of the Three Highest VAS Values of the Hormone Withdrawal-associated Symptoms Pelvic Pain or Headache During Cycle Days 22 to 28 |
36.92; 32.28 | — |
| SECONDARY Change From Baseline to Cycle 13 in the Average of the Three Highest VAS Values of the Hormone Withdrawal-associated Symptoms Pelvic Pain or Headache During Cycle Days 22 to 28 |
45.89; 39.19 | — |
| SECONDARY Number of Days With Bleeding or Spotting in Reference Period 1 |
19.0; 23.7 | — |
| SECONDARY Number of Days With Bleeding or Spotting in Reference Period 2 |
1.3; 18.8 | — |
| SECONDARY Number of Days With Bleeding or Spotting in Reference Period 3 |
14.1; 19.1 | — |
| SECONDARY Number of Days With Bleeding or Spotting in Reference Period 4 |
12.8; 19.4 | — |
| SECONDARY Number of Bleeding / Spotting Episodes in Reference Period 1 |
3.6; 3.7 | — |
| SECONDARY Number of Bleeding / Spotting Episodes in Reference Period 2 |
3.3; 3.4 | — |
| SECONDARY Number of Bleeding / Spotting Episodes in Reference Period 3 |
3.0; 3.3 | — |
| SECONDARY Number of Bleeding / Spotting Episodes in Reference Period 4 |
3.0; 3.7 | — |
| SECONDARY Mean Length of Bleeding / Spotting Episodes in Reference Period 1 |
4.82; 6.20 | — |
| SECONDARY Mean Length of Bleeding / Spotting Episodes in Reference Period 2 |
4.46; 5.71 | — |
| SECONDARY Mean Length of Bleeding / Spotting Episodes in Reference Period 3 |
4.70; 5.85 | — |
| SECONDARY Mean Length of Bleeding / Spotting Episodes in Reference Period 4 |
4.25; 5.65 | — |
| SECONDARY Maximum Length of Bleeding / Spotting Episodes in Reference Period 1 |
7.8; 9.0 | — |
| SECONDARY Maximum Length of Bleeding / Spotting Episodes in Reference Period 2 |
6.2; 7.5 | — |
| SECONDARY Maximum Length of Bleeding / Spotting Episodes in Reference Period 3 |
6.2; 7.4 | — |
| SECONDARY Maximum Length of Bleeding / Spotting Episodes in Reference Period 4 |
5.7; 7.1 | — |
| SECONDARY Difference in Duration Between Longest and Shortest Bleeding / Spotting Episodes in Reference Period 1 |
5.1; 5.1 | — |
| SECONDARY Difference in Duration Between Longest and Shortest Bleeding / Spotting Episodes in Reference Period 2 |
3.3; 3.5 | — |
| SECONDARY Difference in Duration Between Longest and Shortest Bleeding / Spotting Episodes in Reference Period 3 |
3.0; 3.1 | — |
| SECONDARY Difference in Duration Between Longest and Shortest Bleeding / Spotting Episodes in Reference Period 4 |
2.7; 2.8 | — |
| SECONDARY Number of Days With Spotting-only in Reference Period 1 |
9.3; 8.6 | — |
| SECONDARY Number of Days With Spotting-only in Reference Period 2 |
6.8; 6.4 | — |
| SECONDARY Number of Days With Spotting-only in Reference Period 3 |
6.6; 6.3 | — |
| SECONDARY Number of Days With Spotting-only in Reference Period 4 |
5.6; 5.6 | — |
| SECONDARY Number of Spotting-only Episodes in Reference Period 1 |
1.2; 0.5 | — |
| SECONDARY Number of Spotting-only Episodes in Reference Period 2 |
1.0; 0.5 | — |
| SECONDARY Number of Spotting-only Episodes in Reference Period 3 |
0.7; 0.3 | — |
| SECONDARY Number of Spotting-only Episodes in Reference Period 4 |
0.6; 0.2 | — |
| SECONDARY Mean Length of Spotting-only Episodes in Reference Period 1 |
2.64; 2.53 | — |
| SECONDARY Mean Length of Spotting-only Episodes in Reference Period 2 |
2.74; 2.77 | — |
| SECONDARY Mean Length of Spotting-only Episodes in Reference Period 3 |
2.75; 2.44 | — |
| SECONDARY Mean Length of Spotting-only Episodes in Reference Period 4 |
2.77; 2.10 | — |
| SECONDARY Maximum Length of Spotting-only Episodes in Reference Period 1 |
3.3; 2.8 | — |
| SECONDARY Maximum Length of Spotting-only Episodes in Reference Period 2 |
3.2; 3.1 | — |
| SECONDARY Maximum Length of Spotting-only Episodes in Reference Period 3 |
3.5; 2.8 | — |
| SECONDARY Maximum Length of Spotting-only Episodes in Reference Period 4 |
3.2; 2.2 | — |
| SECONDARY Difference in Duration Between Longest and Shortest Spotting-only Episodes in Reference Period 1 |
1.2; 0.5 | — |
| SECONDARY Difference in Duration Between Longest and Shortest Spotting-only Episodes in Reference Period 2 |
1.0; 0.7 | — |
| SECONDARY Difference in Duration Between Longest and Shortest Spotting-only Episodes in Reference Period 3 |
1.4; 0.6 | — |
| SECONDARY Difference in Duration Between Longest and Shortest Spotting-only Episodes in Reference Period 4 |
0.9; 0.2 | — |
| SECONDARY Percentage of Participants With / Without Withdrawal Bleeding at Cycle 1 |
25.0; 12.8; 75.0; 87.2 | — |
| SECONDARY Percentage of Participants With / Without Withdrawal Bleeding at Cycle 3 |
21.0; 7.7; 79.0; 92.3 | — |
| SECONDARY Percentage of Participants With / Without Withdrawal Bleeding at Cycle 6 |
17.7; 8.3; 82.3; 91.7 | — |
| SECONDARY Percentage of Participants With / Without Withdrawal Bleeding at Cycle 13 |
58.2; 19.1; 41.8; 80.9 | — |
| SECONDARY Length of Withdrawal Bleeding Episodes at Cycle 1 |
4.2; 6.0 | — |
| SECONDARY Length of Withdrawal Bleeding Episodes at Cycle 3 |
4.3; 5.8 | — |
| SECONDARY Length of Withdrawal Bleeding Episodes at Cycle 6 |
4.6; 5.7 | — |
| SECONDARY Length of Withdrawal Bleeding Episodes at Cycle 13 |
4.8; 5.5 | — |
| SECONDARY Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 1 |
3.2; 4.0 | — |
| SECONDARY Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 3 |
3.2; 4.2 | — |
| SECONDARY Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 6 |
3.4; 4.0 | — |
| SECONDARY Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 13 |
3.5; 4.1 | — |
| SECONDARY Onset of Withdrawal Bleeding Episodes at Cycle 1 |
4.7; 4.0 | — |
| SECONDARY Onset of Withdrawal Bleeding Episodes at Cycle 3 |
4.3; 3.3 | — |
| SECONDARY Onset of Withdrawal Bleeding Episodes at Cycle 6 |
5.3; 3.1 | — |
| SECONDARY Onset of Withdrawal Bleeding Episodes at Cycle 13 |
1.1; 2.1 | — |
| SECONDARY Percentage of Participants With Presence or Absence of Intracyclic Bleeding at Cycle 1 |
78.3; 91.5; 21.7; 8.5 | — |
| SECONDARY Percentage of Participants With Presence or Absence of Intracyclic Bleeding at Cycle 3 |
79.6; 85.7; 20.4; 14.3 | — |
| SECONDARY Percentage of Participants With Presence or Absence of Intracyclic Bleeding at Cycle 6 |
81.6; 80.3; 18.4; 19.7 | — |
| SECONDARY Percentage of Participants With Presence or Absence of Intracyclic Bleeding at Cycle 13 |
82.7; 93.6; 17.3; 6.4 | — |
| SECONDARY Number of Intracyclic Bleeding Episodes at Cycle 1 |
0.3; 0.1 | — |
| SECONDARY Number of Intracyclic Bleeding Episodes at Cycle 3 |
0.2; 0.2 | — |
| SECONDARY Number of Intracyclic Bleeding Episodes at Cycle 6 |
0.2; 0.2 | — |
| SECONDARY Number of Intracyclic Bleeding Episodes at Cycle 13 |
0.2; 0.1 | — |
| SECONDARY Maximum Length of Intracyclic Bleeding Episodes at Cycle 1 |
6.7; 6.2 | — |
| SECONDARY Maximum Length of Intracyclic Bleeding Episodes at Cycle 3 |
6.6; 4.2 | — |
| SECONDARY Maximum Length of Intracyclic Bleeding Episodes at Cycle 6 |
5.0; 5.2 | — |
| SECONDARY Maximum Length of Intracyclic Bleeding Episodes at Cycle 13 |
3.0; 6.0 | — |
| SECONDARY Number of Intracyclic Bleeding Days at Cycle 1 |
1.5; 0.5 | — |
| SECONDARY Number of Intracyclic Bleeding Days at Cycle 3 |
1.4; 0.7 | — |
| SECONDARY Number of Intracyclic Bleeding Days at Cycle 6 |
0.9; 1.1 | — |
| SECONDARY Number of Intracyclic Bleeding Days at Cycle 13 |
0.5; 0.4 | — |
| SECONDARY Percentage of Participants by Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 1 |
46.2; 50.0; 23.1; 18.8; 15.4; 18.8 | — |
| SECONDARY Percentage of Participants by Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 3 |
47.1; 57.7; 23.5; 15.4; 20.6; 23.1 | — |
| SECONDARY Percentage of Participants by Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 6 |
44.4; 61.3; 25.9; 3.2; 18.5; 19.4 | — |
| SECONDARY Percentage of Participants by Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 13 |
31.6; 57.1; 52.6; 0.0; 10.5; 28.6 | — |
| SECONDARY Percentage of Participants With at Least 1 Intracyclic Bleeding Episode at Cycles 2 to 6 |
53.8; 40.5; 46.2; 59.5 | — |
| SECONDARY Percentage of Participants With at Least 1 Intracyclic Bleeding Episode at Cycles 2 to 13 |
62.0; 49.7; 38.0; 50.3 | — |
| SECONDARY Mean Change From Baseline to Cycle 6 in Psychological General Well-Being Index (PGWBI) |
0.41; 1.10; 0.3; 2.8; 0.18; -1.04 | — |
| SECONDARY Mean Change From Baseline to Cycle 13 in Psychological General Well-Being Index (PGWBI) |
-0.14; -0.18; -1.2; -0.8; -0.65; -0.98 | — |
| SECONDARY Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Physical Health |
1.13; 3.44 | — |
| SECONDARY Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Physical Health |
1.93; 2.13 | — |
| SECONDARY Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Participant Feeling |
0.12; 2.19 | — |
| SECONDARY Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Participant Feeling |
-0.44; 0.39 | — |
| SECONDARY Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Work |
0.54; 0.08 | — |
| SECONDARY Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Work |
-1.38; -1.71 | — |
| SECONDARY Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Household Duties |
1.50; 3.08 | — |
| SECONDARY Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Household Duties |
-0.66; 2.83 | — |
| SECONDARY Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - School/Course Work |
-0.18; 5.13 | — |
| SECONDARY Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - School/Course Work |
-1.97; 4.39 | — |
| SECONDARY Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Leisure Time Activities |
1.22; 2.77 | — |
| SECONDARY Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Leisure Time Activities |
2.72; 2.37 | — |
| SECONDARY Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Social Relationship |
-0.30; 0.41 | — |
| SECONDARY Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Social Relationship |
1.01; 1.75 | — |
| SECONDARY Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - General Activities |
0.56; 1.27 | — |
| SECONDARY Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - General Activities |
0.73; 1.34 | — |
| SECONDARY Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Item Satisfaction |
-0.1; 0.1 | — |
| SECONDARY Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Item Satisfaction |
0.0; 0.1 | — |
| SECONDARY Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Overall Life Satisfaction and Contentment |
-0.1; 0.0 | — |
| SECONDARY Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Overall Life Satisfaction and Contentment |
-0.1; 0.0 | — |
| SECONDARY Percentage of Participants With Improvement in the Investigator's Assessment in Clinical Global Impression (CGI) at Cycle 6 |
21.1; 20.0; 41.5; 25.2; 27.2; 33.5 | — |
| SECONDARY Percentage of Participants With Improvement in the Investigator's Assessment in Clinical Global Impression (CGI) at Cycle 13 |
37.9; 20.3; 32.3; 26.6; 15.3; 27.3 | — |
| SECONDARY Percentage of Participants With Improvement in the Participant's Assessment in Clinical Global Impression (CGI) at Cycle 6 |
25.2; 11.6; 32.7; 30.3; 29.3; 32.2 | — |
| SECONDARY Percentage of Participants With Improvement in the Participant's Assessment in Clinical Global Impression (CGI) at Cycle 13 |
33.9; 17.2; 35.5; 25.0; 16.9; 28.1 | — |
Summary
The objective of the study is to compare the oral contraceptive (OC) SH T00658ID over Ortho Tri-Cyclen Lo administered for 13 cycles to healthy female volunteers between 18 and 50 years of age who request oral contraceptive protection. Subjects on a levonorgestrel (LNG), norgestimate (NGM), norethindrone or norethindrone acetate containing oral contraceptive in a 21-day regimen suffering from hormone withdrawal-associated symptoms such as pelvic pain or headache or both, and willing to continue OC use but to switch to SH T00658ID or Ortho Tri-Cyclen Lo.
Eligibility Criteria
Inclusion Criteria
- Signed and dated informed consent
- Age between 18 and 50 years (inclusive), smokers maximum age of 35 years (inclusive) at Visit 1
- Otherwise healthy female subjects requesting contraception and currently using a LNG, NGM, or norethindrone/norethindrone acetate containing OC in a 21-day regimen and suffering from at least moderate pelvic pain, headache or both defined by an average of the highest 3 values of >/=35 mm on a VAS during cycle days 22-28 (35 mm VAS is the expected standard deviation of the population VAS reduction)
- Normal or clinically insignificant cervical smear not requiring further follow up (a cervical smear has to be taken at screening visit or a normal result has to be documented within the last 6 months before screening) Women with atypical squamous cell of undetermined significance (ASCUS) can be included if they have a negative human papilloma virus (HPV) test result. The laboratory will perform an HPV test if the Pap smear result is ASCUS.
- Able to tolerate ibuprofen and willing to use only ibuprofen supplied by the investigator
Exclusion Criteria
- Pregnancy or lactation (less than three cycles since delivery, abortion, or lactation before start of treatment)
- Body mass index (BMI) >32 kg/m2
- Hypersensitivity to any of the study drug ingredients
- Individuals not willing to consume pork and beef products. Women may be included if they are willing to take the capsules
- Safety relevant laboratory values, provided by the central laboratory, outside inclusion range before start of treatment
- Any diseases or conditions that can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study medication (such as but not limited to duodenal ulcers, gastritis, gastrectomy or gastric resection surgery, or renal compromise)
- Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results
- Any disease or condition that may worsen under hormonal treatment
- Undiagnosed abnormal genital bleeding
- Abuse of alcohol, drugs, or medicines (eg, laxatives)
- Other contraceptive methods
- Any medication that could result in excessive accumulation, impaired metabolism, or altered excretion of the study drug or interfere with the conduct of the study or the interpretation of the results
- Simultaneous participation in another clinical trial prior to study entry that might have an impact on the study objectives at the discretion of the investigator
- Major surgery scheduled for the study period
- Subject is a dependent person, eg: a family member or member of the Investigator's staff
- Inability to cooperate with the study procedures for any reason, including language comprehension, psychiatric illness, inability to get to the study site
Data sourced from ClinicalTrials.gov (NCT00754065). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.