Therapeutic Equivalence Trial of Two Hormonal-IUDs in Patients With Heavy Menstrual Bleeding (LVS-20)

A Multiple Center, Randomised, Parallel Group, Single-blind Clinical Trial, to Assess the Therapeutic Equivalence in Terms of Efficacy and Safety of Test Product (Levosert) and Reference Product (Mirena®) in Patients With Menorrhagia - Phase III (Therapeutic Equivalence).

The primary objective of this study was to compare the efficacy of Test Product (Levosert) vs. Reference Product (Mirena® Bayer-Schering) based on the mean variation of menstrual blood loss volume in women with menorrhagia.

The secondary objectives includes physical and gynaecological examinations, vital signs, clinical laboratory tests including hemoglobin and ferritin measurements, body weight and spontaneously reported adverse events were analysed and compared between Levosert and Mirena® treatment arms. Plasma levels of levonorgestrel (LNG) were also evaluated after various periods of time. The residual amounts of LNG in the devices were finally measured after withdrawal at completion of the study. Plasma levels of LNG and residual amounts of LNG were compared between the two treatment groups. Contraceptive effect of Levosert was estimated by Pearl Index.

Study Overview

• Status: Completed
• Conditions: Heavy Menstrual Bleeding
• Intervention / Treatment: Drug: Levosert-20; Drug: Mirena

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Non-pregnant, non-planning pregnancy, non-lactating non-menopausal females at least 18 years of age.
• Patients with a clinical diagnosis of functional Menorrhagia during the last 6 months.
• Patients who are eligible and able to participate in the trial and who consent to do so in writing after the purpose and nature of the investigation have been explained to them.

Exclusion Criteria:

• History of endometrial ablation or dilatation and/or curettage within the 3 months prior to screening
• Copper - coiled-intrauterine device or LNG releasing IUS use within 2 months prior to screening
• Abnormal liver function or jaundice
• Renal insufficiency
• Other hormonal treatment (sexual steroids),
• Organic causes of abnormal uterine bleeding (presence of endometrial polyps, submucous myomas of any size, or myometrial myomas > than 3 cm, adenomyosis, atypical hyperplasia, carcinoma)
• Abnormal uterine morphology
• Presence of ovarian cyst > 3 cm
• Lower genital tract infection
• Current or recurrent PID (present or recurrent pelvis infection (including history of postpartum endometritis, infected miscarriage) during the past 3 months
• Uncontrolled hypertension
• Congenital or acquired valvular disease (including corrections with prosthetic valves)
• Known or suspected pregnancy
• Known or suspected hormone-dependent tumor
• BMI > 30
• Abnormal Pap smear test or other evidence of cervical/endometrial mancy
• Unexplained amenorrhea
• Known hypersensitivity to device material and/or Levonorgestrel

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levosert-20; Levosert is a LNG-releasing Intrauterine Delivery System (IUS) containing 52 mg of LNG in a cylindrical-shaped reservoir. The reservoir is mounted on the vertical arm of a T-shaped plastic frame and is covered with a release rate controlling membrane.	Drug: Levosert-20
Active Comparator: Mirena®; Mirena® IUS, Bayer-Schering, a LNG-releasing Intrauterine Delivery System (IUS) containing 52 mg of LNG.	Drug: Mirena

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean change from baseline to Year 1 in the mean menstrual blood loss volume measured using the modified Wyatt pictogram in the two treatment groups	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of the plasma levels of LNG (Levonorgestrel) in the 2 treatment groups	up to three years
Comparison of the residual LNG level in the IUS in the 2 treatment groups	up to three years
Mean reduction in menstrual blood loss volume from baseline to intermediate cycles (equivalent to 28-days period)	1 year

Other Outcome Measures

Outcome Measure	Time Frame
Change from baseline to year 1/year 3 in weight in the 2 treatment groups	up to three years
Change from baseline to year 1 / year 3 in hemoglobin in the 2 treatment groups	up to three years
Change from baseline to year 1/year 3 in ferritin in the 2 treatment groups	up to three years
Occurrence in the 2 treatment groups of evaluable untoward drug reactions	up to three years
Contraception level and contraceptive effect in the 2 treatment groups	up to three years

Collaborators and Investigators

• Sponsor: Uteron Pharma S.A.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: September 27, 2012
• First Submitted That Met QC Criteria: September 27, 2012
• First Posted (Estimate): September 28, 2012

Study Record Updates

• Last Update Posted (Estimate): September 28, 2012
• Last Update Submitted That Met QC Criteria: September 27, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Menstruation Disturbances; Uterine Hemorrhage; Hemorrhage; Menorrhagia; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Levonorgestrel
• Other Study ID Numbers: 2007-001564-77