A phase III, double-blind, placebo-controlled, randomized, three-arm parallel, study assessing efficacy and safety of 4 months of diosmin administration for the treatment of lower extremity teleangiectasias and gynoid lipodystrophy (edematous fibrosclerotic panniculopathy commonly known as cellulite)

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2013-004539-57-PL
• Date of registration: 16/12/2013
• Prospective Registration: Yes
• Primary sponsor: ALIO MEDICA Sp. z o.o.
• Public title: A phase III, double-blind, placebo-controlled, randomized, three-arm parallel, study assessing efficacy and safety of 4 months of diosmin administration for the treatment of lower extremity teleangiectasias and gynoid lipodystrophy (edematous fibrosclerotic panniculopathy commonly known as cellulite)
• Scientific title: A phase III, double-blind, placebo-controlled, randomized, three-arm parallel, study assessing efficacy and safety of 4 months of diosmin administration for the treatment of lower extremity teleangiectasias and gynoid lipodystrophy (edematous fibrosclerotic panniculopathy commonly known as cellulite)
• Date of first enrolment: 30/01/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004539-57
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Poland

Contacts

• Name: Coordinating Investigator
• Affiliation: Agnieszka Pszonak

• Name: Coordinating Investigator
• Affiliation: Agnieszka Pszonak

Key inclusion & exclusion criteria

Inclusion criteria:
1. Female subjects (aged = 18 to = 55 years), with body mass index (BMI) 18.50 – 34.99 kg/m2 (the minimum body weight - 50 kg).
2. Availability of the subject in maintaining a stable weight during the study (a variation of less than 8% from baseline body weight is permitted).
3. Having at least 2 separate areas measuring 3 cm x 3 cm of lower extremity telangiectasias as assessed by the Investigator at visit 1a.
4. Having lower extremity telangiectasias less than 1.0 mm in diameter, linear or branching, and red, pink, blue and/or purple in colour, as assessed by the Investigator at visit 1a.
5. Have a cellulite severity scale (CSS) score of = 4 representing mild to severe cellulite severity within the right buttock as assessed by the Investigator at visit 1a and the severity of the cellulite has an important psychological impact for the patient according to the patient..
6. Considering females of childbearing potential: subjects with negative urine pregnancy test at screening and who confirm using one of the effective contraception method: complete abstinence from sexual intercourses or barrier method with spermicide (condom, diaphragm) or intrauterine device (non-hormonal) since at least 4 weeks prior to the first study drug administration or hormonal contraception since at least 6 months prior to the first study drug administration and is willing to use it until completion of the examination at the end of the study.
7. Be willing to refrain from using any other procedure for the treatment of lower extremity spider veins and/or anti-cellulite treatment from screening and throughout the duration of the study.
8. Be willing to maintain habitual diet throughout the trial.
9. Be willing to refrain from making any significant lifestyle changes during the study (exercise regimens, specific diets).
10. Medical history which based on the investigator’s opinion, do not prevent the patient from taking part in the study and use the medicinal product under investigation.
11. Patient understands the study procedures and provides Informed Consent Form signed and dated prior to screening evaluations.
12. Regular menstrual cycle (cycles can range from 21 to 35 days).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Known allergy or hypersensitivity to diosmin or its derivatives and/or to any study product excipients.
2. Any other prior anti-cellulite treatment or body measures treatment or spider veins treatment, 30 days prior to the study (visit 1b).
3. Any prior aesthetic surgery affecting the area to be tested (e.g. liposuction), 3 months before the study (visit 1b), that may interfere with results.
4. Subjects with inflammation or active infection in the area to be tested.
5. Vascular disorder (e.g. phlebitis or varicose veins).
6. Lipoedema or a lymphatic disorder.
7. Coagulation disorders, using anticoagulants or tendency of bruises.
8. History of lower extremity thrombosis or post-thrombosis syndrome.
9. Documented autoimmune disorder such as lupus erythematosus, rheumatoid arthritis.
10. Cardiac insufficiency, asthma or bronchitis.
11. Hypertension.
12. Cutaneous alteration in area to be tested.
13. Subjects with diabetes mellitus any type.
14. Any known significant current or past acute or chronic disease or condition of the: circulatory system, respiratory system, hematopoietic system, alimentary tract, urinary tract, endocrine system, nervous system, musculoskeletal system that may influence the study in the Investigator opinion.
15. Current disease of the alimentary tract, liver or kidneys that may influence the study in the Investigator opinion.
16. Participation in another clinical research study within a period of 30 days prior to randomisation.
17. Abnormal baseline findings, including clinical laboratory results assessed by the Investigator as clinically relevant (CR).
18. Subjects who adhere to a special diet such as low calories (below 1000 kcal).
19. Subjects intensively tanned, or intending to expose the area of study to sun, artificial UV, or self-tanning during the study.
20. Subjects chronically using medication that might lead to disturbance of fluid balance and/or blood circulation (e.g. diuretics, steroids, antidepressants, nonsteroidal anti-inflammatory drugs) and may influence the study in the Investigator opinion.
21. Subjects using hormonal contraception for less than six months.
22. Subjects who smoke.
23. Pregnant, breast-feeding females.
24. Drug and/or alcohol dependence or abuse (use of > 2 units of alcohol a day).
25. Any reason the subject is considered by the Investigator to be an unsuitable candidate to participate in the study



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

lower extremity teleangiectasias and gynoid lipodystrophy (edematous fibrosclerotic panniculopathy commonly known as cellulite)
MedDRA version: 17.0 Level: LLT Classification code 10065339 Term: Cellulite System Organ Class: 100000004858
MedDRA version: 17.0 Level: LLT Classification code 10043193 Term: Telangiectasis System Organ Class: 100000004858

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Trade Name: Diosminex, 500 mg, tabletki powlekane
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: diosmin
CAS Number: 520-27-4
Other descriptive name: DIOSMIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The mean values in a photonumeric scale for grading severity of cellulite after treatment endpoint will be compared between groups.
The mean improvement of lower extremity telangiectasias from baseline to treatment endpoint will be compared between groups.
Treatment endpoint is defined as the last measurement at study completion (4 months) or, if the patient discontinued, as the last observation carried forward.

Secondary Objective: • The secondary objective is to evaluate for all patients
o the efficacy of Diosmin 1 g administered once daily or twice daily compared to placebo in thigh circumference reduction;
o safety of the treatment;
o overall satisfaction based on satisfaction questionnaire;

Timepoint(s) of evaluation of this end point: randomization visit (1b), visit 2 (after 2 months treatment), visit 3 (after 4 months treatment)

Main Objective: The primary objective is to evaluate the efficacy of Diosmin 1 g administered once daily (two 500 mg tablets) or twice daily (four 500 mg tablets) compared to placebo in improvement of lower extremity telangiectasias and in reducing severity of gynoid lipodystrophy, cellulite.

Secondary Outcome(s)

Secondary end point(s): Groups will be compared for:
• The change in a photonumeric scale for grading severity of cellulite after treatment endpoint to baseline values based on blinded photo assessments.
• Reduction of thigh circumference as measured by cm tape measure from baseline to treatment endpoint.
• Tight circumference as measured by cm tape measure at treatment endpoint.
• Assessment of subject’s satisfaction based on satisfaction questionnaire.
• Assessment of safety (see Safety Endpoints)

Timepoint(s) of evaluation of this end point: randomization visit (1b), visit 2 (after 2 months treatment), visit 3 (after 4 months treatment)

Secondary ID(s)

Dio/01/2013

Source(s) of Monetary Support

Alio Medica sp. z o.o.

Narodowe Centrum Badan i Rozwoju