Visanne Study to Assess Safety in Adolescents (VISADO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01283724
First received: January 25, 2011
Last updated: August 12, 2015
Last verified: August 2015
  Purpose

A clinical trial which was designed to demonstrate the safety and efficacy of Visanne (approved in endometriosis for adults) in the adolescent population.


Condition Intervention Phase
Endometriosis
Drug: Dienogest (Visanne, BAY86-5258)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Open Label, Single-arm Study to Investigate the Safety and Efficacy of Daily Oral Administration of 2 mg Dienogest Tablets for the Treatment of Endometriosis in Adolescents Over a Treatment Period of 52 Weeks

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Relative change in bone mineral density (BMD) of the lumbar spine as assessed by dual energy X-ray absorptiometry (DEXA) [ Time Frame: Baseline week 52 ]
    The measurement of BMD by DEXA is the gold standard method for investigation of bone mass.


Secondary Outcome Measures:
  • Relative Percent Change From Baseline in Whole Body Bone Mineral Density (BMD) at Week 52 Assessed by Dual-Energy X-ray Absorptiometry (DEXA) [ Time Frame: Baseline, Week 52 ]
    The measurement of BMD by DEXA is the gold standard method for investigation of bone mass.

  • Change From Baseline in Spinal Lumbar Vertebrae 2 to 4 (L2-L4) Z scores at week 52 [ Time Frame: Baseline, Week 52 ]
    Based on the BMD values and the weight, the age-normalized percentiles (Z-scores) were determined to allow for comparison with historical control groups. "No difference" in comparison with the historical control groups was defined as a Z-score between '-0.5' and '0.5', a lower value was defined as a value below '-0.5', and a higher value above '0.5'.

  • Change From Baseline in Whole Body Z-scores at Week 52 [ Time Frame: Baseline, Week 52 ]
    Based on the BMD values and the weight, the age-normalized percentiles (Z-scores) were determined to allow for comparison with historical control groups. "No difference" in comparison with the historical control groups was defined as a Z-score between '-0.5' and '0.5', a lower value was defined as a value below '-0.5', and a higher value above '0.5'.

  • Percentage of Responders at Week 24 [ Time Frame: Week 24 ]
    Responders were defined as subjects with reduction in pain intensity from baseline of at least 30% in the Visual Analog Scale (VAS) at Week 24. VAS consisted of a 100 unit long straight line, with verbal anchors at either end, representing a continuum of pain intensity. One end of the line with 0 score as "absence of pain" while the other end of the line with 100 score as "unbearable pain". The assessment of pelvic pain on a VAS was done once every 4 weeks till the end of the treatment (Week 52).

  • Change From Baseline in Pelvic Pain Over 52 Weeks Using Modified Biberoglu and Behrman Severity Profile [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
    The cardinal symptoms inlcuded in the modified Biberoglu and Behrman severity profile were pelvic pain, dysmenorrhea, and dyspareunia (the latter only in those subjects having sexual intercourse), analyzed at all visits with symptom severity scores from 0 (none) to 3 (severe). Negative value for change from baseline indicates an improvement. In the listed categories, 'N' signifies those subjects who were evaluable for this measure.

  • Change From Baseline in Dysmenorrhea Over 52 Weeks Using Modified Biberoglu and Behrman Severity Profile [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
    The cardinal symptoms inlcuded in the modified Biberoglu and Behrman severity profile were pelvic pain, dysmenorrhea, and dyspareunia (the latter only in those subjects having sexual intercourse), analyzed at all visits with symptom severity scores from 0 (none) to 3 (severe). Negative value for change from baseline indicates an improvement. In the listed categories, 'N' signifies those subjects who were evaluable for this measure.

  • Percentage of Subjects With Pelvic Pain Over 52 Weeks Using Modified Biberoglu and Behrman Severity Profile [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
    In order to judge therapeutic effectiveness and to compare subjects' complaints, a severity profile score of pelvic pain was assessed using a rating scale: missing; 0 = none; 1 = mild (occasional pelvic discomfort); 2 = moderate (noticeable discomfort for most of the cycle); 3 = severe (requires strong analgesics and persists during cycle when not menstruating) based on the subject's self-assessment of symptoms. In the listed categories, 'N' signifies those subjects who were evaluable for this measure.

  • Percentage of Subjects With Dysmenorrhea Over 52 Weeks Using Modified Biberoglu and Behrman Severity Profile [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
    In order to judge therapeutic effectiveness and to compare subjects' complaints, a severity profile score of dysmenorrhea was assessed using a rating scale: missing; 0 = none; 1 = mild (some loss in work efficiency); 2 = moderate (in bed part of day, occasional loss of work efficiency); 3 = severe (in bed one or more days, incapacitation) based on the subject's self-assessment of symptoms. In the listed categories, 'N' signifies those subjects who were evaluable for this measure.

  • Percentage of Subjects With Dyspareunia Over 52 Weeks Using Modified Biberoglu and Behrman Severity Profile [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
    In order to judge therapeutic effectiveness and to compare subjects' complaints, a severity profile score of dyspareunia was assessed using a rating scale.

  • Percentage of Subjects With Pelvic Tenderness Over 52 Weeks Using Modified Biberoglu and Behrman Severity Profile [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
    In order to judge therapeutic effectiveness and to compare subjects' complaints, a severity profile score of pelvic tenderness was assessed using a rating scale: missing; 0 = none (no pain during intercourse); 1 = mild (minimal tenderness on palpation); 2 = moderate (extensive tenderness on palpation); 3 = severe (unable to palpate because of tenderness) based on the gynecological palpation by the attending physician. In the listed categories, 'N' signifies those subjects who were evaluable for this measure.

  • Percentage of Subjects With Induration Over 52 Weeks Using Modified Biberoglu and Behrman Severity Profile [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
    In order to judge therapeutic effectiveness and to compare subjects' complaints, a severity profile score of induration was assessed using a rating scale: missing; 0 = none (no pain during intercourse); 1 = mild (uterus freely mobile, induration in the cul-de-sac); 2 = moderate (thickened and indurated adnexa and cul-de-sac, restricted uterine mobility); 3 = severe (nodular adnexa and cul-de-sac, uterus frequently frozen) based on the gynecological palpation by the attending physician. In the listed categories, 'N' signifies those subjects who were evaluable for this measure.

  • Percentage of Subjects With Clinical Global Impression (CGI) Scores - Assessed by the Investigator [ Time Frame: Weeks 12, 24, 36, and 52 ]
    The investigator rating scale used in this study was based on the validated CGI scale, which is widely used as a simple tool to assess the overall effect of treatments. The investigator or a sub-investigator rated the total improvement according to the following scale: Score 1 = very much improved; Score 2 =much improved; Score 3 = minimally improved; Score 4 = no change; Score 5 = minimally worse; Score 6 = much worse; Score 7 = very much worse. None of the subjects reported Score 7. In the listed categories, 'N' signifies those subjects who were evaluable for this measure.

  • Percentage of Subjects With Clinical Global Impression (CGI) Scores -Assessed by the Subject [ Time Frame: Weeks 12, 24, 36, 40, and 52 ]
    The subject rating scale used in this study was based on the validated CGI scale, which is widely used as a simple tool to assess the overall effect of treatments. The subject was asked to rate her satisfaction with the study treatment according to the following scale: Score 1 = very much satisfied; Score 2 = much satisfied; Score 3 = minimally satisfied; Score 4 = neither satisfied nor dissatisfied; Score 5 =minimally dissatisfied; Score 6 = much dissatisfied; Score 7 = very much dissatisfied. In the listed categories, 'N' signifies those subjects who were evaluable for this measure.


Enrollment: 111
Study Start Date: March 2011
Study Completion Date: June 2014
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dienogest (Visanne, BAY86-5258)
Subjects received Dienogest tablet orally at a dosage of 2 mg once daily over a period of 52 weeks.
Drug: Dienogest (Visanne, BAY86-5258)
Subjects received Dienogest tablet orally at a dosage of 2 mg once daily over a period of 52 weeks.

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female adolescents after menarche (12 - less than 18 years of age) at screening. For Finland: Adolescents aged 12 - 14 years old who present with clinical features of endometriosis will only be enrolled into the study if their diagnosis of endometriosis has been confirmed by laparoscopy.
  • Dysmenorrhea of at least moderate intensity, with or without chronic pelvic pain, for at least 2 cycles in the previous 4 months and one of the following conditions:

    • Clinically suspected endometriosis based on the presence of pelvic pain incompletely relieved by non steroidal anti-inflammatory drugs and/or oral contraceptives
    • Any abdominal pain associated with ultrasound findings suggestive of endometriosis (abdominal, vaginal or rectal; only after additional specific consent and assent)
    • Failure of surgical treatment for endometriosis (with cyclic or chronic pelvic pain of at least 4 months duration postsurgery)
    • Threshold for endometriosis-associated pelvic pain (EAPP) score: at least 30 on a 100 units visual analog scale retrospectively evaluated at screening for the last 4 weeks

Exclusion Criteria:

  • Absence of endometriosis at laparoscopy
  • Previous application of hormonal agents including oral contraceptives within 2 months, progestins, danazol within 3 months, and Gonadotropin Releasing Hormone (GnRH) agonists within 6 months prior to start of treatment
  • Chronic pelvic pain that might be related to genitourinary disease or to chronic or recurrent gastrointestinal disease, including irritable bowel syndrome (defined as a disease characterized by pain relieved by defecation and irregular defecation patterns lasting at least 3 months)
  • Clinically established need for primary surgical treatment of endometriosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01283724

Locations
Austria
St. Pölten, Niederösterreich, Austria, 3100
Linz, Oberösterreich, Austria, 4020
Graz, Steiermark, Austria, 8044
Graz, Austria, 8010
Innsbruck, Austria, 6020
Wien, Austria, 1060
Wien, Austria, 1090
Czech Republic
Brno, Czech Republic, 625 00
Ceske Budejovice, Czech Republic, 37001
Pisek, Czech Republic, 39701
Praha, Czech Republic, 13000
Praha 2, Czech Republic
Finland
Espoo, Finland, 02100
Helsinki, Finland, 00100
Turku, Finland, 20100
France
Angers Cedex 01, France, 49033
Le Kremlin Bicetre, France, 94275
Paris, France, 75018
Rouen, France, 76031
Germany
Erlangen, Bayern, Germany, 91054
Oldenburg, Niedersachsen, Germany, 26121
Westerstede, Niedersachsen, Germany, 26655
Münster, Nordrhein-Westfalen, Germany, 48149
Lübeck, Schleswig-Holstein, Germany, 23538
Berlin, Germany, 12587
Berlin, Germany, 12200
Berlin, Germany, 10117
Berlin, Germany, 13509
Berlin, Germany, 14129
Berlin, Germany, 14193
Hamburg, Germany, 20357
Spain
Benidorm, Alicante, Spain, 03503
Vigo, Pontevedra, Spain, 36209
Sevilla, Spain, 41013
Sevilla, Spain, 41014
Valencia, Spain, 46017
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01283724     History of Changes
Other Study ID Numbers: 13788, 2009-017169-53
Study First Received: January 25, 2011
Last Updated: August 12, 2015
Health Authority: Austria: Agency for Health and Food Safety
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Spain: Spanish Agency of Medicines

Keywords provided by Bayer:
Endometriosis
DEXA
Adolescent
Safety
Efficacy
Post-menarche

Additional relevant MeSH terms:
Endometriosis
Genital Diseases, Female
Dienogest
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Contraceptive Agents
Contraceptive Agents, Female
Contraceptive Agents, Male
Contraceptives, Oral
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015