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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-002449-40 | EudraCT Number | ||
| MK-8175A/MK-8342B-057 | Other Identifier | Merck |
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The study investigates four vaginal ring groups with respect to relief of primary dysmenorrhea, and should identify at least one vaginal ring that shows clinically relevant treatment efficacy in relief of primary dysmenorrhea.
The study investigates four vaginal ring groups with respect to relief of primary dysmenorrhea, and should identify at least one vaginal ring that shows clinically relevant treatment efficacy in relief of primary dysmenorrhea. The intake of ibuprofen rescue medication and the impact on daily life is investigated: change from baseline data of these two variables will be compared between each of the four active ring groups, separately, and the placebo ring group. Furthermore, the study assesses the measurement characteristics and psychometric properties of a newly developed Dysmenorrhea Daily Dairy. Vaginal bleeding pattern and general safety and tolerability will also be evaluated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NOMAC-E2 700/300 mcg | Experimental | NOMAC-E2 700/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
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| NOMAC-E2 900/300 mcg | Experimental | NOMAC-E2 900/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
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| ENG-E2 100/300 mcg | Experimental | ENG-E2 100/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
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| ENG-E2 125/300 mcg | Experimental | ENG-E2 125/300 mcg will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
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| Placebo |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nomegestrol acetate contraceptive vaginal ring (NOMAC-CVR) | Drug | Either 700 or 900 mcg NOMAC and 300 mcg E2 intravaginal ring for two 28-day cycles |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Mean Menstrual Cramping Pain Score Through Cycle 2 | The Mean Menstrual Cramping Pain score was calculated as the average of the three highest daily menstrual cramping scores (item #3 of the Menstrual Distress Questionnaire: "Cramps") in the baseline cycle and treatment Cycle 2, respectively. The daily menstrual cramping pain score was based on five pain categories: none (0); mild (1); moderate (2); strong (3); and severe (4). In case of absence of withdrawal bleeding, or onset of menstruation, the mean of the three highest menstrual cramping pain scores recorded within Days 21-28 was used for analysis. The Mean Menstrual Cramping Pain Score in the baseline or subsequent cycles could range from 0 (none) to 4 (severe). | Baseline and Day 29 to 56 (Cycle 2) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Total Mean Impact Score Through Cycle 2 | Total Mean Impact Score is the mean of the sum of the daily responses to questions 6, 8, 9, and 10 in the Dysmenorrhea Daily e-Dairy, as recorded within the menstrual cramping pain analysis window. These questions assessed how much interference there was from pelvic cramping pain on work/school activities (Q6), physical activities (Q8), social/leisure activities (Q9) and sleep (Q10). Each question was rated on a 5-point (0-4) scale, with 0 being "not at all", 1 "slightly", 2 "moderately", 3 "quite a bit" and 4 "extremely". The total mean impact score could thus range from 0 (lowest possible impact) to 16 (highest possible impact). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30439359 | Derived | Fox MC, Klipping C, Nguyen AM, Frenkl TL, Cruz SM, Wang Y, Korver T. A phase 2b multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of vaginal rings containing nomegestrol acetate or etonogestrel and 17beta-estradiol in the treatment of women with primary dysmenorrhea. Contraception. 2019 Feb;99(2):125-130. doi: 10.1016/j.contraception.2018.10.009. Epub 2018 Nov 12. |
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| ID | Title | Description |
|---|---|---|
| FG000 | NOMAC-E2 700/300 mcg | NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| FG001 | NOMAC-E2 900/300 mcg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo Comparator |
Placebo will be administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
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| Etonogestrel containing contraceptive vaginal ring (ENG-CVR) | Drug | Either 100 or 125 mcg ENG and 300 mcg E2, intravaginally for two 28-day cycles |
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| Placebo | Drug | Placebo to match vaginal ring, intravaginally for two 28-day cycles |
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| Ibuprofen | Drug | Ibuprofen 400 mg will be dispensed throughout the entire study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose is 3200 mg (8 tablets) |
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| Baseline and Day 29 to 56 (Cycle 2) |
| Change From Baseline in Number of Ibuprofen Tablets Taken Through Cycle 2 | Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries. | Baseline and Day 29 to 56 (Cycle 2) |
| Change From Baseline in Number of Days of Ibuprofen Intake Through Cycle 2 | Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries. | Baseline and Day 29 to 56 (Cycle 2) |
NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
| FG002 | ENG-E2 100/300 mcg | ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| FG003 | ENG-E2 125/300 mcg | ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| FG004 | Placebo | Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| Treated |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | NOMAC-E2 700/300 mcg | NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| BG001 | NOMAC-E2 900/300 mcg | NOMAC-E2 900/300 mcg administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| BG002 | ENG-E2 100/300 mcg | ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| BG003 | ENG-E2 125/300 mcg | ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| BG004 | Placebo | Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Mean Menstrual Cramping Pain Score Through Cycle 2 | The Mean Menstrual Cramping Pain score was calculated as the average of the three highest daily menstrual cramping scores (item #3 of the Menstrual Distress Questionnaire: "Cramps") in the baseline cycle and treatment Cycle 2, respectively. The daily menstrual cramping pain score was based on five pain categories: none (0); mild (1); moderate (2); strong (3); and severe (4). In case of absence of withdrawal bleeding, or onset of menstruation, the mean of the three highest menstrual cramping pain scores recorded within Days 21-28 was used for analysis. The Mean Menstrual Cramping Pain Score in the baseline or subsequent cycles could range from 0 (none) to 4 (severe). | All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Menstrual Cramping Pain Score | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Day 29 to 56 (Cycle 2) |
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| Secondary | Change From Baseline in Total Mean Impact Score Through Cycle 2 | Total Mean Impact Score is the mean of the sum of the daily responses to questions 6, 8, 9, and 10 in the Dysmenorrhea Daily e-Dairy, as recorded within the menstrual cramping pain analysis window. These questions assessed how much interference there was from pelvic cramping pain on work/school activities (Q6), physical activities (Q8), social/leisure activities (Q9) and sleep (Q10). Each question was rated on a 5-point (0-4) scale, with 0 being "not at all", 1 "slightly", 2 "moderately", 3 "quite a bit" and 4 "extremely". The total mean impact score could thus range from 0 (lowest possible impact) to 16 (highest possible impact). | All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Total Mean Impact Score | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Day 29 to 56 (Cycle 2) |
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| Secondary | Change From Baseline in Number of Ibuprofen Tablets Taken Through Cycle 2 | Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries. | All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Number of Ibuprofen Tablets Taken | Posted | Least Squares Mean | 95% Confidence Interval | Ibuprofen tablets | Baseline and Day 29 to 56 (Cycle 2) |
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| Secondary | Change From Baseline in Number of Days of Ibuprofen Intake Through Cycle 2 | Participants were provided with ibuprofen 400 mg tablets at the screening visit to be taken throughout the study as needed as rescue medication for treating menstrual cramping pain. The maximum daily ibuprofen dose was 3200 mg (8 tablets). Participants were instructed to take the provided ibuprofen, and no other medications, for the relief of menstrual cramping pain, and to record their ibuprofen usage in their e-Diaries. | All randomized participants in whom a vaginal ring was inserted and who had at least one baseline or one post-baseline value for Number of Days of Ibuprofen Intake | Posted | Least Squares Mean | 95% Confidence Interval | Days of ibuprofen intake | Baseline and Day 29 to 56 (Cycle 2) |
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Up to 64 days
The Safety Analysis was based on all randomized participants in whom a vaginal ring was inserted.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NOMAC-E2 (700/300 mcg) | NOMAC-E2 700/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days | 0 | 86 | 12 | 86 | ||
| EG001 | NOMAC-E2 (900/300 mcg) | NOMAC-E2 900/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. | 1 | 91 | 11 | 91 | ||
| EG002 | ENG-E2 (100/300 mcg) | ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. | 0 | 86 | 14 | 86 | ||
| EG003 | ENG-E2 (125/300 mcg) | ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. | 1 | 85 | 7 | 85 | ||
| EG004 | Placebo | Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. | 0 | 90 | 11 | 90 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
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| Impulse-control disorder | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Breast pain | Reproductive system and breast disorders | MedDRA 16.0 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
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The investigator agrees to provide to the Sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including slides and texts of oral or other public presentations and texts of any transmission through any electronic media that report results of the trial. The Sponsor has the right to review and comment with respect to publications, abstracts, slides, and manuscripts, as wells as comment on the data analysis and presentation.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D004412 | Dysmenorrhea |
| ID | Term |
|---|---|
| D008599 | Menstruation Disturbances |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D017699 | Pelvic Pain |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D007052 | Ibuprofen |
| ID | Term |
|---|---|
| D010666 | Phenylpropionates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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| Male |
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| Difference in Least Squares Means |
| -0.6 |
| 2-Sided |
| 95 |
| -0.9 |
| -0.2 |
| Superiority or Other (legacy) |
| cLDA | < 0.001 | Difference in Least Squares Means | -0.8 | 2-Sided | 95 | -1.1 | -0.4 | Superiority or Other (legacy) |
| cLDA | < 0.001 | Difference in Least Squares Means | -0.5 | 2-Sided | 95 | -0.9 | -0.2 | Superiority or Other (legacy) |
| OG002 |
| ENG-E2 100/300 mcg |
ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| OG003 | ENG-E2 125/300 mcg | ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| OG004 | Placebo | Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
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ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
| OG003 | ENG-E2 125/300 mcg | ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| OG004 | Placebo | Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
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ENG-E2 100/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days.
| OG003 | ENG-E2 125/300 mcg | ENG-E2 125/300 mcg was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
| OG004 | Placebo | Placebo was administered for two 28-day treatment periods, each period (cycle) consisting of 21 days of vaginal ring use followed by 7 vaginal ring-free days. |
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