Clinical trial • Endocrinology|Other

LETROZOLE for Polycystic ovary syndrome

Clinical trial of LETROZOLE for Polycystic ovary syndrome.

Overview

Trial Therapeutic Area
Endocrinology|Other
Trial Disease
Polycystic ovary syndrome
Drug Modality
Small molecule|Peptide/protein/enzyme

Key dates

Initial CTIS Submission Date
10-03-2025
First CTIS Authorization Date
30-05-2025

Trial design

Randomised, comparator: human menopausal gonadotrophins (solution for injection, subcutaneous) and follitropin alfa (solution for injection in pre-filled pen, subcutaneous). product metadata lists max daily dose up to 225 (doseuom: mg or iu) and max total amounts over treatment period (maxtotaldoseamount 3150 over maxtreatmentperiod 14 days) as provided in product entries.-controlled trial across 30 sites in Netherlands.

Randomised
Yes
Comparator
Comparator: HUMAN MENOPAUSAL GONADOTROPHINS (solution for injection, subcutaneous) and FOLLITROPIN ALFA (solution for injection in pre-filled pen, subcutaneous). Product metadata lists max daily dose up to 225 (doseUom: mg or IU) and max total amounts over treatment period (maxTotalDoseAmount 3150 over maxTreatmentPeriod 14 days) as provided in product entries.
Target Sample Size
816
Trial Duration For Participant
240

Eligibility

Recruits 816 Vulnerable populations were not selected for this trial. Participants are adult women aged 18-42 years; 'Inability to give informed consent' is listed as an exclusion. Consent must be provided by the participant; no assent procedures for minors are applicable..

Pregnancy Exclusion
Additional contra-indications reported in the SPC are: Hypersensitivity to the active substance, during pregnancy and breast feeding
Vulnerable Population
Vulnerable populations were not selected for this trial. Participants are adult women aged 18-42 years; 'Inability to give informed consent' is listed as an exclusion. Consent must be provided by the participant; no assent procedures for minors are applicable.

Inclusion criteria

  • {"criterion_text":"- Couples or single women with childwish"}
  • {"criterion_text":"- Diagnosed PCOS (normogonadotropic anovulation with hyperandrogenaemia (diagnosed clinically by the presence of excessive acne, androgenic alopecia, or hirsutism or by elevated serum levels of total, bioavailable, or free testosterone or dehydroepiandrosterone sulfate) or polycystic ovaries on ultrasound)"}
  • {"criterion_text":"- Age 18-42 years"}
  • {"criterion_text":"- Ovulatory for six cycles on letrozole treatment"}

Exclusion criteria

  • {"criterion_text":"- Contra-indication to letrozole"}
  • {"criterion_text":"- Total motile sperm count (VCM) < 3 million"}
  • {"criterion_text":"- Known bilateral fallopian tube pathology or occlusion (patients with at least one patent fallopian tube are eligible)"}
  • {"criterion_text":"- Major medical morbidity (e.g. poorly controlled Type I or Type II diabetes, known liver disease or dysfunction based on serum liver enzyme testing, renal disease or abnormal serum renal function)"}
  • {"criterion_text":"- Inability to give informed consent"}
  • {"criterion_text":"- Additional contra-indications reported in the SPC are: Hypersensitivity to the active substance, during pregnancy and breast feeding"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Pregnancy within 8 months after randomization, leading to a live birth","definition_or_measurement_approach":"Pregnancy occurring within 8 months after randomization that results in a live birth (timeframe and outcome-based endpoint as stated)."}

Secondary endpoints

  • {"endpoint_text":"- Clinical pregnancy, ongoing pregnancy, biochemical pregnancy loss and miscarriage rates within 8 months after randomisation","definition_or_measurement_approach":"Rates of clinical pregnancy, ongoing pregnancy, biochemical pregnancy loss and miscarriage measured within 8 months after randomisation."}
  • {"endpoint_text":"- For each participant, the number of treatment cycles initiated, completed and cancelled are evaluated within 8 months after randomisation","definition_or_measurement_approach":"Count of treatment cycles initiated, completed and cancelled per participant within 8 months after randomisation."}
  • {"endpoint_text":"- Of all achieved (ongoing) pregnancies occurring within 8 months after randomization (including spontaneous pregnancies) the following outcomes are assessed; multiple pregnancy rate, time to pregnancy, pregnancy complications, perinatal outcomes, type of delivery and outcomes","definition_or_measurement_approach":"Assessment of pregnancy outcomes for pregnancies within 8 months after randomization, including multiple pregnancy rate, time to pregnancy, complications, perinatal outcomes, delivery type and neonatal outcomes."}
  • {"endpoint_text":"- Side effects, compliance and smoking behavior during treatment assessed through telephone appointment and questionnaires sent out at 3 months and 8 months after randomisation.","definition_or_measurement_approach":"Safety and behaviour data collected via telephone appointments and questionnaires at 3 and 8 months after randomisation."}
  • {"endpoint_text":"- Quality of life and mental health assessed at time of randomization, and at 3 months and 8 months after randomization, using the PCOS-QoL questionnaire and the HADS questionnaire","definition_or_measurement_approach":"PCOS-QoL and HADS questionnaires administered at baseline (randomization), 3 months and 8 months to measure QoL and mental health."}
  • {"endpoint_text":"- Budget impact and cost-effectiveness analyses using live birth rates","definition_or_measurement_approach":"Economic analyses (budget impact and cost-effectiveness) using live birth rates as effectiveness measure."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
816
Recruitment Window Months
60
Consent Approach
Informed consent obtained from the participant (adult women 18-42). 'Inability to give informed consent' is an exclusion. A subject information sheet and informed consent form are provided (document L1_SIS and ICF); documents and trial materials have translations (protocol synopsis available in EN and NL), indicating availability in Dutch and English.

Methods

  • Website texts and online materials (K2_ NL_Recruitment material_Text for websites) targeting women with PCOS and childwish (Netherlands).
  • Poster materials (K2_ NL_Recruitment material_Poster) targeting clinic patients and visitors (Netherlands).
  • Animation video and script (K2_Recruitment material_Script animatievideo / NL animation) for online dissemination (Netherlands).

Geography

Total Number Of Sites
30
Total Number Of Participants
816

Netherlands

Earliest CTIS Part Ii Submission Date
22-05-2025
Latest Decision Or Authorization Date
13-05-2026
Processing Time Days
356
Number Of Sites
30
Number Of Participants
816

Sites

Site Name
Diakonessenhuis Stichting
Department Name
Obstetrics & Gynecology
Principal Investigator Name
K.L. Deurloo
Principal Investigator Email
wetenschapsbureau@diakhuis.n
Contact Person Name
K.L. Deurloo
Contact Person Email
wetenschapsbureau@diakhuis.n
Site Name
Groene Hart Ziekenhuis
Department Name
Obstetrics & Gynecology
Principal Investigator Name
C.A.H. Janssen
Principal Investigator Email
ineke.janssen@ghz.nl
Contact Person Name
C.A.H. Janssen
Contact Person Email
ineke.janssen@ghz.nl
Site Name
Fertiliteitskliniek Twente B.V.
Department Name
Obstetrics & Gynecology
Principal Investigator Name
M.F.G. Verberg
Principal Investigator Email
m.verberg@fertiliteitskliniektwente.nl
Contact Person Name
M.F.G. Verberg
Site Name
Ikazia Ziekenhuis
Department Name
Obstetrics & Gynecology
Principal Investigator Name
B. Torrenga
Principal Investigator Email
b.torrenga@ikazia.nl
Contact Person Name
B. Torrenga
Contact Person Email
b.torrenga@ikazia.nl
Site Name
Universitair Medisch Centrum Groningen
Department Name
Obstetrics & Gynecology
Principal Investigator Name
A.E.P. Cantineau-Gielkens
Principal Investigator Email
a.e.p.cantineau@umcg.nl
Contact Person Name
A.E.P. Cantineau-Gielkens
Contact Person Email
a.e.p.cantineau@umcg.nl
Site Name
Maxima Medisch Centrum
Department Name
Obstetrics & Gynecology
Principal Investigator Name
B.J. Van der Knoop
Principal Investigator Email
b.vanderknoop@mmc.nl
Contact Person Name
B.J. Van der Knoop
Contact Person Email
b.vanderknoop@mmc.nl
Site Name
Noordwest Ziekenhuisgroep Stichting
Department Name
Obstetrics & Gynecology
Principal Investigator Name
M.C. De Hundt
Principal Investigator Email
m.d.hundt@nwz.nl
Contact Person Name
M.C. De Hundt
Contact Person Email
m.d.hundt@nwz.nl
Site Name
Zuyderland Medisch Centrum Stichting
Department Name
Obstetrics & Gynecology
Principal Investigator Name
G. De Krom
Principal Investigator Email
g.dekrom@zuyderland.nl
Contact Person Name
G. De Krom
Contact Person Email
g.dekrom@zuyderland.nl
Site Name
Amphia Hospital
Department Name
Obstetrics & Gynecology
Principal Investigator Name
J. Visser
Principal Investigator Email
VisserJ8@amphia.nl
Contact Person Name
J. Visser
Contact Person Email
VisserJ8@amphia.nl
Site Name
Deventer Ziekenhuis
Department Name
Obstetrics & Gynecology
Principal Investigator Name
J. van den Berg
Principal Investigator Email
wetenschapsbureau@dz.nl
Contact Person Name
J. van den Berg
Contact Person Email
wetenschapsbureau@dz.nl
Site Name
ETZ Elisabeth
Department Name
Obstetrics & Gynecology
Principal Investigator Name
I.A.J. van Rooij
Principal Investigator Email
i.vanrooij@etz.nl
Contact Person Name
I.A.J. van Rooij
Contact Person Email
i.vanrooij@etz.nl
Site Name
Treant Ziekenhuiszorg Stichting
Department Name
Obstetrics & Gynecology
Principal Investigator Name
S.B.M. Gaykema
Principal Investigator Email
s.gaykema@treant.nl
Contact Person Name
S.B.M. Gaykema
Contact Person Email
s.gaykema@treant.nl
Site Name
Universitair Medisch Centrum Utrecht
Department Name
Obstetrics & Gynecology
Principal Investigator Name
T. Dahhan
Principal Investigator Email
t.dahhan@umcutrecht.nl
Contact Person Name
T. Dahhan
Contact Person Email
t.dahhan@umcutrecht.nl
Site Name
Catharina Ziekenhuis Stichting
Department Name
Obstetrics & Gynecology
Principal Investigator Name
M.M.E. Van Rumste
Principal Investigator Email
minouche.v.rumste@catharinaziekenhuis.nl
Contact Person Name
M.M.E. Van Rumste
Site Name
Albert Schweitzer Ziekenhuis
Department Name
Obstetrics & Gynecology
Principal Investigator Name
M.L. Bandell
Principal Investigator Email
bandellm@asz.nl
Contact Person Name
M.L. Bandell
Contact Person Email
bandellm@asz.nl
Site Name
Amsterdam UMC Stichting
Department Name
Obstetrics & Gynecology
Principal Investigator Name
M. Goddijn
Principal Investigator Email
m.goddijn@amsterdamumc.nl
Contact Person Name
M. Goddijn
Contact Person Email
m.goddijn@amsterdamumc.nl
Site Name
Sint Franciscus Vlietland Groep Stichting
Department Name
Obstetrics & Gynecology
Principal Investigator Name
S.C.J.P. Gielen
Principal Investigator Email
wetenschapsbureau@franciscus.nl
Contact Person Name
S.C.J.P. Gielen
Site Name
Elkerliek Ziekenhuis
Department Name
Obstetrics & Gynecology
Principal Investigator Name
J. Kortekaas
Principal Investigator Email
jc.kortekaas@elkerliek.nl
Contact Person Name
J. Kortekaas
Contact Person Email
jc.kortekaas@elkerliek.nl
Site Name
Radboud universitair medisch centrum Stichting
Department Name
Obstetrics & Gynecology
Principal Investigator Name
L.E.E. Van der Houwen
Principal Investigator Email
lisette.vanderhouwen@radboudumc.nl
Contact Person Name
L.E.E. Van der Houwen
Site Name
Rijnstate Ziekenhuis Stichting
Department Name
Obstetrics & Gynecology
Principal Investigator Name
F. Janse
Principal Investigator Email
fjanse@rijnstate.nl
Contact Person Name
F. Janse
Contact Person Email
fjanse@rijnstate.nl
Site Name
Nij Geertgen Centrum voor vruchtbaarheid B.V.
Department Name
Gynecology
Principal Investigator Name
K. Fleischer
Principal Investigator Email
kathrin.fleischer@nijgeertgen.nl
Contact Person Name
K. Fleischer
Site Name
Tergooiziekenhuizen
Department Name
Obstetrics & Gynecology
Principal Investigator Name
C. De Koning
Principal Investigator Email
CdeKoning@tergooi.nl
Contact Person Name
C. De Koning
Contact Person Email
CdeKoning@tergooi.nl
Site Name
Ziekenhuis Gelderse Vallei Stichting
Department Name
Obstetrics & Gynecology
Principal Investigator Name
A.J.C.M. Van Dongen
Principal Investigator Email
dongena@zgv.nl
Contact Person Name
A.J.C.M. Van Dongen
Contact Person Email
dongena@zgv.nl
Site Name
Canisius Wilhelmina Ziekenhuis
Department Name
Obstetrics & Gynecology
Principal Investigator Name
C.F. van Heteren
Principal Investigator Email
c.v.heteren@cwz.nl
Contact Person Name
C.F. van Heteren
Contact Person Email
c.v.heteren@cwz.nl
Site Name
Jeroen Bosch Ziekenhuis Stichting
Department Name
Obstetrics & Gynecology
Principal Investigator Name
J.P. De Bruin
Principal Investigator Email
j.d.bruin@jbz.nl
Contact Person Name
J.P. De Bruin
Contact Person Email
j.d.bruin@jbz.nl
Site Name
Stichting OLVG
Department Name
Obstrics & Gynecology
Principal Investigator Name
H.R. Verhoeve
Principal Investigator Email
H.R.Verhoeve@olvg.nl
Contact Person Name
H.R. Verhoeve
Contact Person Email
H.R.Verhoeve@olvg.nl
Site Name
Frisius MC
Department Name
Obstetrics & Gynecology
Principal Investigator Name
D.A.M. Perquin
Principal Investigator Email
denise.perquin@frisiusmc.nl
Contact Person Name
D.A.M. Perquin
Contact Person Email
denise.perquin@frisiusmc.nl

Sponsor

Primary sponsor

Full Name
Amsterdam UMC Stichting
Organisation Type
Patient organisation/association
Country Of Registered Address
Netherlands

Investigational products

Investigational Product Name
LETROZOLE
Active Substance
LETROZOLE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
7.5 mg per day
Investigational Product Name
HUMAN MENOPAUSAL GONADOTROPHINS
Active Substance
HUMAN MENOPAUSAL GONADOTROPHINS
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS
Route
SUBCUTANEOUS
Maximum Dose
225 mg per day (max daily amount stated in product entry)
Investigational Product Name
FOLLITROPIN ALFA
Active Substance
FOLLITROPIN ALFA
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS
Route
SUBCUTANEOUS
Maximum Dose
225 IU per day (max daily amount stated in product entry)

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