TIRZEPATIDE for Overweight|Obesity|Polycystic ovary syndrome

Inclusion criteria

• {"criterion_text":"- Written informed consent to participate in this clinical trial in accordance with local regulations and the ethical review board governing this clinical trial\n- Biochemical signs of hyperandrogenism with total testosterone in upper 95th Percentile AND free androgen index (FAI) > ULN and/or clinical signs of hyperandrogenism\n- Hormonal contraceptive naïve or not on hormonal contraceptives six months prior to screening, willing to be without hormonal contraceptives for the duration of the clinical trial and to perform safe alternate contraception (barrier methods) during the 72-week IMP intake period and 30 days after the last dose of IMP\n- Subject is motivated, capable, and willing to self-inject IMP, as required for this protocol\n- Subject is motivated, capable, and willing to follow trial procedures for the duration of the clinical trial, including, but not limited to lifestyle, dietary and exercise advice\n- Subject is motivated, capable, and willing to complete trial diaries and required questionnaires\n- Females aged 18 – 45 years of childbearing potential\n- At least 3 years post-menarche and premenopausal\n- BMI ≥ 27 kg/m²\n- Previous diagnosis of PCOS\n- Oligomenorrhea or secondary amenorrhea with irregular periods (defined as cycle length less than 21 or more than 35 days or < 8 cycles per year); within the last 10 years (if currently receiving hormonal contraceptive treatment) OR over the last year in the absence of hormonal contraceptive treatment"}

Exclusion criteria

• {"criterion_text":"- Subjects without legal capacity who are unable to understand the nature, scope, significance and consequences of this clinical trial\n- Prior diagnosis of diabetes mellitus other forms than type 2\n- In case of diabetes mellitus type 2: on DPP-4 inhibitors, GLP-1R agonist, a dual/triple incretin agonist (up to 6 months prior to screening)\n- In case of diabetes mellitus type 2: on sulfonylureas or insulin (basal and/or bolus)\n- In case of diabetes mellitus type 2: with uncontrolled diabetes (HbA1c > 8.5%)\n- In case of diabetes mellitus type 2: with non-proliferative diabetic retinopathy requiring acute treatment\n- In case of diabetes mellitus type 2: with diabetic maculopathy\n- Current or prior treatment (up to 6 months prior to screening) with GLP-1R agonist or a dual incretin agonist for obesity or other indications\n- Use of inositol formulations (up to 6 months prior to screening)\n- Congenital adrenal hyperplasia (CAH, classic and non-classic forms)\n- Thyroid, pituitary, and/or adrenal disease (if not appropriately treated)\n- Subjects with a physical or psychiatric condition which at the investigator’s discretion may put the subject at risk, may confound the trial results, or may interfere with the subject’s participation in this clinical trial\n- Hyperprolactinaemia\n- Known history of benign intrauterine lesions\n- Hysterectomy\n- Known history of hypersensitivity against tirzepatide or excipients\n- Known personal or family history of medullary thyroid cancer or subjects with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)\n- Elevated calcitonin levels as determined by the laboratory during screening: ≥ 20 ng/L, if eGFR ≥ 60 mL/min/1.73 m2 ≥ 35 ng/L, if eGFR < 60 mL/min/1.73 m2\n- Known secondary cause of obesity (i.e., Cushing syndrome) or monogenetic or syndromic forms of obesity (i.e., melanocortin 4 receptor deficiency or Prader Willi Syndrome)\n- Known history of acute or chronic pancreatitis\n- Previous or planned bariatric surgery or endoscopic and/or device-based therapy for obesity\n- Simultaneous participation in another clinical trial, or participation in a clinical trial taking an investigational product, up to 30 days after last IMP in-take in that clinical trial\n- Known or persistent abuse of medication, drugs or alcohol\n- History of an active or untreated malignancy or being in remission from a clinically significant malignancy for less than 5 years\n- Prior diagnosis of severe renal impairment or measured as estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² during screening\n- Acute or chronic hepatitis, signs and symptoms of any other liver disease other than non-alcoholic fatty liver disease, or alanine aminotransferase (ALT) level > 3.0 X the upper limit of normal, as determined by the laboratory during screening\n- History of gastric emptying abnormality (e.g., gastroparesis, gastric outlet obstruction or chronic dependence on drugs that significantly affect gastric emptying)\n- Current (positive pregnancy test, e.g., ß-HCG test in urine / serum) or planned pregnancy during the 72-week IMP intake period and 30 days after the last dose of IMP, or nursing women"}

Primary endpoints

• {"endpoint_text":"- Mean menstrual bleeding ratio (number of menstrual bleedings divided by treatment period in months) during the last 52 weeks of treatment, assessed at 72 weeks after randomization","definition_or_measurement_approach":"Mean menstrual bleeding ratio defined as number of menstrual bleedings divided by treatment period in months; assessed at 72 weeks after randomization (last 52 weeks of treatment)."}
• {"endpoint_text":"- Mean change in menstrual bleeding ratio from baseline, calculated at 72 weeks after randomization (with baseline defined as mean menstrual bleeding ratio during the 6 months before randomization)","definition_or_measurement_approach":"Change from baseline (baseline = mean menstrual bleeding ratio during the 6 months before randomization) calculated at 72 weeks after randomization."}

Secondary endpoints

• {"endpoint_text":"- Total number of biochemically confirmed ovulatory events (within 24 weeks after completed dose titration) measured by weekly serum progesterone","definition_or_measurement_approach":"Measured by weekly serum progesterone; counted within 24 weeks after completed dose titration."}
• {"endpoint_text":"- Percentage of subjects who achieve a normalization of menstrual cycle (defined as cycle length longer than 21 and less than 35 days or > 8 cycles per year) at 72 weeks after randomization","definition_or_measurement_approach":"Normalization defined as cycle length >21 and <35 days or >8 cycles per year; assessed at 72 weeks after randomization."}
• {"endpoint_text":"- Serum Anti Müllerian Hormone (AMH)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Early follicular total testosterone, estradiol, progesterone, sex hormone-binding globulin (SHBG), DHEA-S and androstenedione, LH and FSH","definition_or_measurement_approach":"Measured in early follicular phase; specific assays not specified."}
• {"endpoint_text":"- Calculated free androgen index (FAI) and calculated free testosterone","definition_or_measurement_approach":""}
• {"endpoint_text":"- Mean and percentage change in body weight and % of subjects achieving ≥ 5%, ≥ 10%, ≥ 15%, ≥ 20% of body weight loss from randomization","definition_or_measurement_approach":"Absolute and percent change from randomization; responder thresholds at ≥5, ≥10, ≥15, ≥20% weight loss."}
• {"endpoint_text":"- Mean change in body composition (measured by BIA) from randomization","definition_or_measurement_approach":"Measured by bioelectrical impedance analysis (BIA)."}
• {"endpoint_text":"- Mean change in waist circumference (cm) and waist to hip ratio from randomization","definition_or_measurement_approach":""}
• {"endpoint_text":"- Mean change in fasting glucose (mg/dl) from randomization","definition_or_measurement_approach":""}
• {"endpoint_text":"- Mean change in HbA1c (%) from randomization","definition_or_measurement_approach":""}
• {"endpoint_text":"- Mean change in systemic insulin sensitivity from randomization derived by fasting and oGTT data: QUICKI, HOMA-IR, Matsuda's Insulin-sensitivity index","definition_or_measurement_approach":"Derived from fasting and oral glucose tolerance test (oGTT) data using QUICKI, HOMA-IR, and Matsuda index."}
• {"endpoint_text":"- Mean change in fasting triglycerides (mg/dl), total and LDL cholesterol (mg/dl), and triglyceride-to-HDL cholesterol ratio from randomization","definition_or_measurement_approach":""}
• {"endpoint_text":"- Mean change in liver enzymes and non-invasive biomarkers, Fatty Liver Index (FLI), FIB4-score, liver stiffness and fat content from randomization","definition_or_measurement_approach":"Includes FLI, FIB4, liver stiffness and fat content measures; specific techniques not detailed."}
• {"endpoint_text":"- Mean change in SBP (mmHg) and DBP (mmHg) from randomization","definition_or_measurement_approach":""}
• {"endpoint_text":"- Mean change in hs-CRP (mg/l) from randomization","definition_or_measurement_approach":""}
• {"endpoint_text":"- Mean change in test scores from randomization: 36-Item Short Form Survey (SF-36), Patient Global Impression of Severity (PGI-S), European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L5L), Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ)","definition_or_measurement_approach":"Patient-reported outcome instruments: SF-36, PGI-S, EQ-5D-5L, PCOSQ."}

Germany

Earliest CTIS Part Ii Submission Date

03-07-2025

Latest Decision Or Authorization Date

25-07-2025

Processing Time Days

22

Number Of Sites

5

Number Of Participants

198

Primary sponsor

Full Name

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Organisation Type

Educational Institution

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"Lilly Deutschland GmbH","duties_or_roles":"Monetary support","organisation_type":""}