VISADO: Visanne Study to Assess Safety in Adolescents

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT01283724

Collaborator

(none)

111

Enrollment

Locations

Arm

Duration (Months)

3.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Endometriosis	Drug: Dienogest (Visanne, BAY86-5258)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

111 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Mar 1, 2011

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

Outcome Measures

Primary Outcome Measures

Relative change in bone mineral density (BMD) of the lumbar spine as assessed by dual energy X-ray absorptiometry (DEXA) [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) [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 17 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Locations

	City	State	Country	Postal Code
1	St. Pölten	Niederösterreich	Austria	3100
2	Linz	Oberösterreich	Austria	4020
3	Graz	Steiermark	Austria	8044
4	Graz		Austria	8010
5	Innsbruck		Austria	6020
6	Wien		Austria	1060
7	Wien		Austria	1090
8	Brno		Czech Republic	625 00
9	Ceske Budejovice		Czech Republic	37001
10	Pisek		Czech Republic	39701
11	Praha 2		Czech Republic
12	Praha		Czech Republic	13000
13	Espoo		Finland	02100
14	Helsinki		Finland	00100
15	Turku		Finland	20100
16	Angers Cedex 01		France	49033
17	Le Kremlin Bicetre		France	94275
18	Paris		France	75018
19	Rouen		France	76031
20	Erlangen	Bayern	Germany	91054
21	Oldenburg	Niedersachsen	Germany	26121
22	Westerstede	Niedersachsen	Germany	26655
23	Münster	Nordrhein-Westfalen	Germany	48149
24	Lübeck	Schleswig-Holstein	Germany	23538
25	Berlin		Germany	10117
26	Berlin		Germany	12200
27	Berlin		Germany	12587
28	Berlin		Germany	13509
29	Berlin		Germany	14129
30	Berlin		Germany	14193
31	Hamburg		Germany	20357
32	Benidorm	Alicante	Spain	03503
33	Vigo	Pontevedra	Spain	36209
34	Sevilla		Spain	41013
35	Sevilla		Spain	41014
36	Valencia		Spain	46017