Effects on Hemostasis, Lipids, Carbohydrate Metabolism, Adrenal & Thyroid Function of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing LNG-EE (292004)(COMPLETED)(P05764)

This study has been completed.

Sponsor:

Information provided by:

Schering-Plough

ClinicalTrials.gov Identifier:

NCT00511355

First received: August 2, 2007

Last updated: October 10, 2011

Last verified: October 2011

History of Changes

Results First Received: July 28, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Prevention
Condition:	Contraception
Interventions:	Drug: NOMAC-E2 Drug: Levonorgestrel and Ethinyl Estradiol

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE	Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.

Participant Flow: Overall Study

	NOMAC-E2	LNG-EE
STARTED	60	61
COMPLETED	53	52
NOT COMPLETED	7	9
Adverse Event	4	4
Pregnancy Wish	1	0
Lost to Follow-up	2	1
Other Reason	0	1
Pre-treatment (serious) adverse event	0	1
Withdrawal of informed consent	0	1
Other reason pre-treatment	0	1

Baseline Characteristics

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Reporting Groups

	Description
NOMAC-E2	All-participants-treated group. Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles
LNG-EE	All-participants-treated group. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 6 consecutive 28-day cycles
Total	Total of all reporting groups

Baseline Measures

	NOMAC-E2	LNG-EE	Total
Number of Participants [units: participants]	60	58	118
Age ^[1] [units: years] Mean ± Standard Deviation	28.2 ± 8.2	29.1 ± 7.8	28.7 ± 8.0
Gender ^[1] [units: participants]
Female	60	58	118
Male	0	0	0

[1]	All-participants-treated group. For the LNG-EE arm, this population excludes 3 subjects who were randomized but not treated.

Outcome Measures

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1. Primary:

Serum Concentration of Prothrombin Fragments 1 + 2 [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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2. Primary:

Serum Concentration of D-Dimer [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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3. Primary:

Activated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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Measure Type	Primary
Measure Title	Activated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based)
Measure Description	Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). APC resistance ratio (ETP-based) measures the anticoagulation response of plasma to APC after activation of the extrinsic coagulation pathway. An increase in the ratio indicates a reduced responsiveness to APC. Each cycle consists of 28 days.
Time Frame	Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Safety Issue	Yes

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-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles.
LNG-EE	Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.

Measured Values

	NOMAC-E2	LNG-EE
Number of Participants Analyzed [units: participants]	60	58
Activated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based) [units: Ratio] Mean ± Standard Deviation
Baseline (n=59 NOMAC-E2; n=58 LNG-EE)	0.80 ± 0.33	0.83 ± 0.40
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)	1.14 ± 0.45	1.99 ± 0.76

Statistical Analysis 1 for Activated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based)

Groups ^[1]	All groups
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	<.0001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	P-value compares the change from baseline to Cycle 6 between treatment groups.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No correction for multiple testing was made.

4. Primary:

Serum Concentration of Clotting Factor VIIa [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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5. Primary:

Serum Concentration of Clotting Factor VIIc [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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6. Primary:

Serum Concentration of Clotting Factor VIII [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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7. Primary:

Serum Concentration of Clotting Factor II [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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8. Primary:

Serum Concentration of Antithrombin III [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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9. Primary:

Serum Concentration of Protein S (Free) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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10. Primary:

Serum Concentration of Protein S (Total) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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11. Primary:

Serum Concentration of Protein C [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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12. Primary:

APC Resistance Ratio (Activated Partial Thromboplastin Time [APTT]-Based) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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13. Primary:

Serum Concentration of Sex Hormone Binding Globulin (SHBG) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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14. Primary:

Serum Concentration of C-Reactive Protein (CRP) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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15. Primary:

Serum Concentration of Total Cholesterol [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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16. Primary:

Serum Concentration of High Density Lipoprotein (HDL)-Cholesterol [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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17. Primary:

Serum Concentration of HDL2-cholesterol [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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18. Primary:

Serum Concentration of HDL3-cholesterol [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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19. Primary:

Serum Concentration of Low Density Lipoprotein (LDL)-Cholesterol [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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20. Primary:

Serum Concentration of Apolipoprotein A-1 [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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21. Primary:

Serum Concentration of Apolipoprotein B [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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22. Primary:

Serum Concentration of Lipoprotein(a) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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23. Primary:

Serum Concentration of Total Triglycerides [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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24. Primary:

Area Under the Curve Over 3 Hours (AUC3) for Glucose (Oral Glucose Tolerance Test [OGTT]) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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25. Primary:

Incremental AUC3 for Glucose (OGTT) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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26. Primary:

AUC3 for Insulin (OGTT) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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27. Primary:

Incremental AUC3 for Insulin (OGTT) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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28. Primary:

Serum Concentration of Hemoglobin Type A1c (HbA1c) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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29. Primary:

Serum Concentration of Total Cortisol [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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30. Primary:

Serum Concentration of Corticosteroid Binding Globulin (CBG) [ Time Frame: Baseline to Cycle 6 (between Days 15 and 21 of the cycle) ]

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31. Primary:

Serum Concentration of Thyroid Stimulating Hormone (TSH) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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32. Primary:

Serum Concentration of Free Thyroxine (T4) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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33. Primary:

Serum Concentration of Thyroxin Binding Globulin (TBG) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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34. Secondary:

Serum Concentration of Total Testosterone [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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35. Secondary:

Serum Concentration of Free Testosterone [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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36. Secondary:

Serum Concentration of Dehydroepiandrosterone Sulphate (DHEAS) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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37. Secondary:

Serum Concentration of Androstenedione [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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38. Secondary:

Serum Concentration of Dihydrotestosterone (DHT) [ Time Frame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle) ]

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39. Secondary:

Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) [ Time Frame: 6 cycles ]

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40. Secondary:

Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting [ Time Frame: Every 28-day cycle for 6 cycles ]

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41. Secondary:

Number of Participants With an Occurrence of Absence of Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 6 cycles ]

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42. Secondary:

Number of Participants With an Occurrence of Breakthrough Bleeding [ Time Frame: Every 28-day cycle for 6 cycles ]

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43. Secondary:

Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) [ Time Frame: Every 28-day cycle for 6 cycles ]

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44. Secondary:

Number of Participants With an Occurrence of Early Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 6 cycles ]

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45. Secondary:

Number of Participants With an Occurrence of Continued Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 5 cycles ]

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46. Secondary:

Average Number of Breakthrough Bleeding/Spotting Days [ Time Frame: Every 28-day cycle for 6 cycles ]

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47. Secondary:

Average Number of Withdrawal Bleeding/Spotting Days [ Time Frame: Every 28-day cycle for 6 cycles ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The SPONSOR recognizes the right of the investigator(s) to publish, but all publications must be based on data validated and released by the SPONSOR. Any such scientific paper, presentation, or other communication concerning the clinical trial will first be submitted to the SPONSOR, at least six weeks ahead of estimated publication or presentation, for consent, which shall not be withheld unreasonably.

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
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Results Point of Contact:

Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp
e-mail: ClinicalTrialsDisclosure@merck.com

No publications provided

Responsible Party:	Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00511355 History of Changes
Other Study ID Numbers:	Organon Protocol No. 292004, P05764
Study First Received:	August 2, 2007
Results First Received:	July 28, 2011
Last Updated:	October 10, 2011
Health Authority:	Finland: Finnish Medicines Agency

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