A Clinical Trial of Tirzepatide (LY3298176) in Subjects With Overweight or Obesity and PCOS-related Ovarian Dysfunction (PERIODS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19], Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

9 Dec 2025 → ongoing

Decision date (initial)

2025-07-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Lilly Deutschland GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for improvement of ovarian dysfunction as defined by menstrual irregularity in overweight or obesity-related PCOS

Secondary objectives 20

1. Key secondary: To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for improvement of ovarian dysfunction as defined by ovulation frequency in overweight or obesity-related PCOS
2. To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for improvement of ovarian dysfunction and hyperandrogenism
3. To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for improvement of body weight measures
4. To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for glycemic status and lipid profile
5. To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for Metabolic dysfunction-associated steatotic liver disease (MASLD)
6. To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for blood pressure
7. To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for systemic meta-inflammation
8. To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for patient reported outcomes
9. Exploratory (72 weeks): To evaluate the dose-dependent efficacy of tirzepatide (5 mg, 10 mg, and 15 mg) compared to placebo regarding improvement of ovarian dysfunction as defined by menstrual irregularity and ovulation frequency
10. Exploratory (72 weeks): To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for PCOM Morphology
11. Exploratory (72 weeks): To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for improvement of clinical hyperandrogenism
12. Exploratory (72 weeks): To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for improvement of hyperglycemia in women with type 2 diabetes
13. Exploratory (124 weeks): To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for maintained improvement of ovarian function and hyperandrogenism at 52 weeks after drug discontinuation
14. Exploratory (124 weeks): To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for successful fertilization
15. Exploratory (124 weeks): To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for body weight maintenance at 52 weeks after drug discontinuation
16. Exploratory (124 weeks): To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for maintenance of glycemic status and lipid profile at 52 weeks after drug discontinuation
17. Exploratory (124 weeks): To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for metabolic dysfunction-associated steatotic liver disease (MASLD)
18. Exploratory (124 weeks): To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for blood pressure
19. Exploratory (124 weeks): To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for systemic meta-inflammation
20. Exploratory (124 weeks): To demonstrate that tirzepatide in its maximum tolerated dose is superior to placebo for patient reported outcomes

Conditions and MedDRA coding

Overweight or Obesity

Regulatory references

Plan to share IPD

Yes

IPD plan description

Individual subject data will be available. Individual subject data (including data dictionaries) that under-lie results concerning primary or secondary endpoints reported in a published scientific article will be shared on demand after deidentification. Furthermore, the following documents will be made available at least: Trial Protocol and Informed Consent Form. The data will be shared immediately following publication and ending 10 years following publication. Data are made available to researchers after a methodologically sound scientific proposal has been submitted to the Coordinating Investigator, and a steering committee consisting of the Coordinating Investigator, the representative of the Coordinating Investigator, and an authorized SZB member has approved the proposal. The data will be shared to achieve aims in the approved proposal. Proposals should be directed to [email protected]. To gain access, data requestors will need to sign a data access agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Written informed consent to participate in this clinical trial in accordance with local regulations and the ethical review board governing this clinical trial
2. Subject is motivated, capable, and willing to self-inject IMP, as required for this protocol
3. 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
4. Subject is motivated, capable, and willing to complete trial diaries and required questionnaires
5. Females aged 18 – 45 years of childbearing potential
6. At least 3 years post-menarche and premenopausal
7. BMI ≥ 27 kg/m²
8. Previous diagnosis of PCOS
9. 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
10. Biochemical signs of hyperandrogenism with total testosterone in upper 95th Percentile AND free androgen index (FAI) > ULN and/or clinical signs of hyperandrogenism
11. 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

Exclusion criteria 28

1. Subjects without legal capacity who are unable to understand the nature, scope, significance and consequences of this clinical trial
2. 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
3. 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
4. Known or persistent abuse of medication, drugs or alcohol
5. History of an active or untreated malignancy or being in remission from a clinically significant malignancy for less than 5 years
6. Prior diagnosis of severe renal impairment or measured as estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² during screening
7. 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
8. History of gastric emptying abnormality (e.g., gastroparesis, gastric outlet obstruction or chronic dependence on drugs that significantly affect gastric emptying)
9. 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
10. Prior diagnosis of diabetes mellitus other forms than type 2
11. 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)
12. In case of diabetes mellitus type 2: on sulfonylureas or insulin (basal and/or bolus)
13. In case of diabetes mellitus type 2: with uncontrolled diabetes (HbA1c > 8.5%)
14. In case of diabetes mellitus type 2: with non-proliferative diabetic retinopathy requiring acute treatment
15. In case of diabetes mellitus type 2: with diabetic maculopathy
16. 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
17. Use of inositol formulations (up to 6 months prior to screening)
18. Congenital adrenal hyperplasia (CAH, classic and non-classic forms)
19. Thyroid, pituitary, and/or adrenal disease (if not appropriately treated)
20. Hyperprolactinaemia
21. Known history of benign intrauterine lesions
22. Hysterectomy
23. Known history of hypersensitivity against tirzepatide or excipients
24. Known personal or family history of medullary thyroid cancer or subjects with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
25. 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
26. 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)
27. Known history of acute or chronic pancreatitis
28. Previous or planned bariatric surgery or endoscopic and/or device-based therapy for obesity

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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
2. 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)

Secondary endpoints 16

1. Total number of biochemically confirmed ovulatory events (within 24 weeks after completed dose titration) measured by weekly serum progesterone
2. 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
3. Serum Anti Müllerian Hormone (AMH)
4. Early follicular total testosterone, estradiol, progesterone, sex hormone-binding globulin (SHBG), DHEA-S and androstenedione, LH and FSH
5. Calculated free androgen index (FAI) and calculated free testosterone
6. Mean and percentage change in body weight and % of subjects achieving ≥ 5%, ≥ 10%, ≥ 15%, ≥ 20% of body weight loss from randomization
7. Mean change in body composition (measured by BIA) from randomization
8. Mean change in waist circumference (cm) and waist to hip ratio from randomization
9. Mean change in fasting glucose (mg/dl) from randomization
10. Mean change in HbA1c (%) from randomization
11. Mean change in systemic insulin sensitivity from randomization derived by fasting and oGTT data: QUICKI, HOMA-IR, Matsuda's Insulin-sensitivity index
12. Mean change in fasting triglycerides (mg/dl), total and LDL cholesterol (mg/dl), and triglyceride-to-HDL cholesterol ratio from randomization
13. Mean change in liver enzymes and non-invasive biomarkers, Fatty Liver Index (FLI), FIB4-score, liver stiffness and fat content from randomization
14. Mean change in SBP (mmHg) and DBP (mmHg) from randomization
15. Mean change in hs-CRP (mg/l) from randomization
16. 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)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Sponsor organisation

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Address

Venusberg-Campus 1, Venusberg Venusberg

City

Bonn

Postcode

53127

Country

Germany

Scientific contact point

Organisation

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Contact name

Prof. Dr. med. Wiebke Fenske

Public contact point

Organisation

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Contact name

Prof. Dr. med. Wiebke Fenske

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications