Primary DysmenorrheaPhase 3NCT06211049
Efficacy of Vitex Agnus-castus BNO 1095 (20 mg) in Women With Primary Dysmenorrhea
A Phase 3 study testing Vitex agnus-castus BNO 1095 (20 mg) in people with Primary Dysmenorrhea, run by Bionorica SE at 34 sites in 6 countries.
Trial summary
In this Phase III study, the herbal product Vitex agnus-castus BNO 1095 20 mg will be tested. The sponsor would like to find out if treatment with Vitex agnus-castus BNO 1095 20 mg may improve the cramping pain before or during menstruation (primary dysmenorrhea) (without an organic cause) in women and if this… Read more about this study
- Who is it for?
- Ages 18 to 49 years, women only
- Conditions the study is for
- Primary Dysmenorrhea
- What is being tested?
- Vitex agnus-castus BNO 1095 (20 mg)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 335 participants
- Where
- 34 sitesin 6 countries
- Study dates
- 12 Dec 2023to 23 Jul 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women aged 18-49 years who have the capacity for consenting
- Patient has been informed of the nature, scope, and relevance of the clinical trial, voluntary agrees in participation and the trial provisions, and has duly signed the approved informed consent form (ICF)
- Diagnosed primary dysmenorrhea
- If patients take pain relief medication for primary dysmenorrhea, this medication should be taken unchanged with regard to application form and kind of medication including strength during the Screening as well as during the first three treatment cycles.
- Note: Medication (drugs) for primary dysmenorrhea as mono- or combination therapy in form of tablets/capsules regularly used by the patient before Screening is allowed to be used as standard pain relief medication during the trial apart from non-medication methods. A complete list of allowed pain relief medication is attached to the protocol.
- This medication should be taken by the patient at least for 1 cycle before Screening guaranteeing a stable intake of this medication in total for 3 cycles before randomization.
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- Patients with a regular menstrual cycle duration of ≥24 to ≤38 days
- Patients agreeing to use one of the following contraception methods throughout the trial:
- Bilateral tubal occlusion
- Vasectomized partner (provided that the partner is the sole sexual partner of the woman and has received medical assessment of the surgical success)
- Sexual abstinence Abstinence is only accepted as true abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal) is not an acceptable method of contraception
- Male or female condom with or without spermicide
- Cap, diaphragm, or sponge with spermicide
Who cannot join
- A patient will not be eligible for inclusion if any of the following criteria applies:
- Non-menstruating women
- Clinically diagnosed secondary dysmenorrhea (e.g., fibroids, uterine adenomyosis, endometriosis, pelvic inflammation, ovarian pathologies, or other pelvic diseases)
- Dysmenorrhea resulting from the use of an intrauterine device
- Use of hormonal contraceptives (oral, intravaginal, transdermal, injectable, implantable), intrauterine device, or intrauterine hormone-releasing system within 6 months prior to the trial and not willing to waive it during the entire trial period
- Any surgical treatments in the past (e.g., due to myoma) that may cause pain, adhesions or scarring in the lower abdomen Note: Further diagnostic examination (e.g., laparoscopy for differential diagnosis, exclusion of endometriosis) if deemed necessary by the investigator will be outside the trial protocol and reimbursement
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- Known or suspected gastrointestinal or urological conditions that may cause abdominal and/or pelvic pain, such as colitis, appendicitis, irritable bowel syndrome, cholelithiasis, interstitial cystitis, cystitis, urolithiasis, and other conditions that, according to the investigator's judgement, are not suitable for the trial
- Known or suspected gynecological complaints e.g., premenstrual abdominal pain, deep dyspareunia, uterine fibroids and polyps, or chronic pain (abdominal, dorsal, urogenital)
- Known instable diseases e.g., psychiatric, cardiovascular, or endocrine disorders
- Body mass index <18.5 or >34.9 kg/m² at Screening
- Known or suspected acute infection of gonorrhea, syphilis and/or chlamydia at Screening
- Current or past estrogen sensitive cancer or pituitary disorder that, in the investigator's opinion, would make the patient not suitable for the trial
- Women who are breastfeeding, pregnant (positive pregnancy test at Screening), or planning to become pregnant during the trial
- Fewer than 3 menstrual cycles before Screening following delivery, abortion, miscarriage, or lactation
- Current severe physical or mental illness
- Patient does not agree to avoid daily smoking
- History of alcohol, drug, or medicine abuse within 1 year prior to Screening, or positive for drugs or medicines of abuse in the laboratory analysis performed at Screening
- Patients with hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
- Hypersensitivity to Vitex agnus-castus, lactose or any of the excipients of the IMP or to any ingredients of the standard pain relief medication
- Patients committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
- Employees of the sponsor or site staff or direct relatives of the site staff
- Legal incapacity or limited legal capacity
- Patients not able to follow trial instructions or assessments or to participate in the trial for the whole duration of approximately 7 months or unable to understand written and verbal instruction, in particular regarding the risks and inconveniences that the patients will be exposed to during participation in the clinical trial
- Participation in another interventional clinical trial during the last month before Screening
- Use of Vitex agnus-castus containing preparation or product within the last 3 months before Screening
- Current intake or intake within the last 4 weeks before Screening of dopamine agonists, dopamine antagonists, estrogens, or antiestrogens that would make the patient not suitable for the trial
Trial locations and contacts
34 sites in 6 countries.
34 sites in 6 countries
Germany12 sites
Praxis Dr. Noel
Aachen, 52072
Klinische Forschung Berlin-Mitte GmbH
Berlin, 10117
Frauenarztpraxis Dipl. med. Andrea Heweker, Praxis für Gynäkologie
Bernburg, 06406
Klinische Forschung Dresden GmbH
Dresden, 01069
Praxis Geseke
Geseke, 59590
Frauenarztpraxis Dr. Inka Kiesche
Halle, 06110
Klinische Forschung Hamburg GmbH
Hamburg, 20253
Frauenarzt-Praxis Dr. med. Klaus Peters
Hamburg, 22159
Klinische Forschung Hannover Mitte GmbH
Hanover, 30159
Klinische Forschung Karlsruhe GmbH
Karlsruhe, 76137
Klinische Forschung Schwerin GmbH
Schwerin, 19055
Frauenarzt in Stolberg - Wolfgang Clemens
Stolberg, 52222
Czechia7 sites
Centrum ambulantní gynekologie a primární péče s.r.o.
Brno-střed, 60200
Fakultní nemocnice Brno, Gynekologickoporodnická Klinika, Centrum asistované reprodukce CAR 01 Brno
Brno-střed, 60200
GYNEKOLOGIE CHEB s.r.o.
Cheb, 35002
NEUMED gynekologická ambulance s.r.o
Olomouc, 77900
MUDr. Martina Marešová Rosenbergová s.r.o.
Pilsen, 30100
Centrum gynekologické rehabilitace s.r.o
Písek, 39701
Gyncare MUDr. Michael Švec s.r.o.
Plzeň 2-Slovany, 32600
Hungary6 sites
Clinexpert Kft.
Budapest, 1033
Óbudai Egészségügyi Centrum Kft.
Budapest, 1036
Zatik Med Kft.
Debrecen, 4024
BKS Research Kft.
Hatvan, 3000
AXON Kereskedelmi Es Szolgaltato Kft.
Kecskemét, 6000
IPR Hungary Kft.
Miskolc, 3530
Poland5 sites
Centrum Medyczne Mikołowska dr Adam Sipiński
Katowice, 40-065
Silmedic Sp. z o.o.
Katowice, 40-282
Nzoz Profi-Med
Lublin, 20-880
Centrum Badawcze Panaceum Agnieszka Brzezicka, Magdalena Lenkiewicz Sp. z o.o.
Malbork, 82-200
Państwowy Instytut Medyczny Ministerstwa Spraw Wewnętrznych i Administracji, Klinika Położnictwa, Chorób Kobiecych i Ginekologii Onkologicznej
Warsaw, 02-507
Austria2 sites
Medizinische Universität Innsbruck, Department Frauenheilkunde, Universitätsklinik für Gynäkologische Endokrinologie und Reproduktionsmedizin
Innsbruck, 6020
Medizinische Universität Wien, Universitätsklinik für Frauenheilkunde, Klinische Abteilung für Gynäkologische Endokrinologie und Reproduktionsmedizin
Vienna, 1090
Sweden2 sites
Karolinska University Hospital, WHO-centre
Stockholm, SE-171 76
Umeå University, Dep. of Clinical Sciences, Obstetrics and Gynecology
Umeå, SE-907 37
About this study
In this Phase III study, the herbal product Vitex agnus-castus BNO 1095 20 mg will be tested.
The sponsor would like to find out if treatment with Vitex agnus-castus BNO 1095 20 mg may improve the cramping pain before or during menstruation (primary dysmenorrhea) (without an organic cause) in women and if this treatment is safe. It is tested, if the pelvic pain and other symptoms during menstruation improve in patients who are treated with Vitex agnus-castus BNO 1095 20 mg and if therefore the standard treatments for primary dysmenorrhea, for example pain relief medications will not have to be increased.
The study has 2 treatment groups. Patients in one group will receive Vitex agnus-castus BNO 1095 20 mg, and patients in the other group will receive a placebo. Placebo tablets look like Vitex agnus-castus BNO 1095 20 mg tablets but have no active ingredient. Patients will be randomly assigned (like tossing a coin) to one of the 2 groups (this process is called randomization). The chance for the patients to receive Vitex agnus-castus BNO 1095 is 50%. Neither the patients nor the investigators know which product the patients are taking (this method is known as "double-blind").
Read the detailed description
This is a randomized, placebo-controlled, double-blind, multicenter, phase III clinical trial to investigate the efficacy and safety of investigational medicinal product (IMP) Vitex agnus-castus BNO 1095 20 mg in women with primary dysmenorrhea.
The clinical trial will be conducted in Austria, Czech Republic, Germany, Hungary, Poland and Sweden.
About 390 patients will be screened so that about 300 patients (150 patients per treatment group) will be randomized.
Vitex agnus-castus BNO 1095 20 mg is extracted from the fruits of the plant Vitex agnus-castus also called monk's pepper or chaste tree. Vitex agnus-castus BNO 1095 20 mg is currently marketed for the treatment of the premenstrual syndrome (PMS) which means repeated occurrence of physical, behavioral and psychological symptoms the days before the onset of menstruation, but it is not authorized for the treatment of primary dysmenorrhea.
The study has 2 treatment groups. Patients in one group will receive Vitex agnus-castus BNO 1095 20 mg, and patients in the other group will receive a placebo. Patients will be randomly assigned 1:1 to one of the 2 groups. The chance to receive Vitex agnus-castus BNO 1095 is 50%. The study is double blinded, neither the patients nor the investigators know which product the patients are taking.
The study will last about 7 months for each patient. There will be 5 visits at the study site, and in addition the patients will receive 3 phone calls from the study site. On average, each study site visit will take about 2 hours and each phone call about half an hour.
The trial will include 3 phases: a screening and run-in phase of up to 2 menstrual cycles, a treatment phase of 4 menstrual cycles and a follow-up phase of 1 menstrual cycle. The length of each phase depends on the length of women's menstrual cycle. If their menstrual cycle is 28 days, the screening and run-in phase will take up to 59 days (slightly more than 2 menstrual cycles), the treatment phase 113 days (about 4 menstrual cycles), and the follow-up phase 28 days (1 menstrual cycle).
The main objective of this study is to determine if primary dysmenorrhea improves in women treated with Vitex agnus-castus BNO 1095 20 mg compared to placebo over a treatment duration of 3 menstrual cycles (cramping windows of Cycles 3-5).
Vitex agnus-castus BNO 1095 20 mg or placebo tablets are taken orally (means by mouth) once a day during the treatment phase.
If a patient usually takes pain relief medication for primary dysmenorrhea, the patient is allowed to continue taking this pain relief medication during study participation.
The patients will complete the dysmenorrhea daily diary (DysDD) every day in the evening. Depending on her bleeding status, the diary includes questions about menstrual bleeding, pieces of sanitary protection used, severity of the worst pain or cramps in the pelvic area on a numerical rating scale (NRS), intake of pain relief medication, and impact on daily life in an electronic diary (handheld device).
Additionally, the dysmenorrhea associated symptoms nausea, vomiting, diarrhea, fatigue, weakness, fainting, and headache will be assessed by the patients on a NRS in the electronic diary on Days 1-3 of the menstrual cycle. Migraine will be assessed by the investigator at the clinical trial visits. The patient and investigator will assess the efficacy of treatment on a 5-point verbal rating scale at the end of treatment and at the end of the study (EoS).
- Conditions
- Primary Dysmenorrhea
- Being tested
- Vitex agnus-castus BNO 1095 (20 mg), Placebo
- Keywords
- Vitex agnus-castus, Menstrual pain
- Medical subject headings
- Dysmenorrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitex agnus-castus BNO 1095 (20 mg)Drug
1 tablet once daily for about 4 menstrual cycles (cramping windows of Cycles 3-6) (i.e.,113 days in case of a 28-day menstrual cycle).
PlaceboDrug
1 tablet once daily for about 4 menstrual cycles (cramping windows of Cycles 3-6) (i.e.,113 days in case of a 28-day menstrual cycle).
| Study group | Role | What they receive |
|---|---|---|
| Vitex agnus-castus BNO 1095 (20 mg) | Experimental | 1 tablet once daily for about 4 menstrual cycles (cramping windows of Cycles 3-6) (i.e., 113 days in case of a 28-day menstrual cycle). Receives: Drug: Vitex agnus-castus BNO 1095 (20 mg) |
| Placebo | Placebo comparator | 1 tablet once daily for about 4 menstrual cycles (cramping windows of Cycles 3-6) (i.e., 113 days in case of a 28-day menstrual cycle). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who respond to treatment defined as: a) a ≥3-point reduction in the peak pelvic pain score and b) no increase in the number of standard pain relief medication
Response to treatment will be determined by comparing the peak pelvic pain score (using an 11-point numeric rating scale (NRS, scale ranging from 0 (no symptom) to 10 (extreme severity of symptom) of the dysmenorrhea daily diary (DysDD) assessments) made during the cramping window of Cycle 5 with those made at Baseline and by comparing the assessments of number of tablets or capsules of standard pain relief medication taken during the cramping window of Cycle 5 with those taken at Baseline.
Measured: Change from Baseline (28 days prior to randomization) to the cramping window of Cycle No. 5 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Secondary outcomes (20)
Proportion of patients who respond to treatment defined as: a) a ≥3-point reduction in the peak pelvic pain score and b) no increase in the number of standard pain relief medication in the cramping window of Cycles 3, 4, and 6 compared to Baseline
Response to treatment will be determined by comparing the peak pelvic pain score (using an 11-point numeric rating scale (NRS, scale ranging from 0 (no symptom) to 10 (extreme severity of symptom) of the dysmenorrhea daily diary (DysDD) assessments) made during the cramping window of Cycles No. 3, 4 and 6 with those made at Baseline and by comparing the assessments of number of tablets or capsules of standard pain relief medication taken during the cramping window of Cycles No. 3, 4 and 6 with those taken at Baseline.
Measured: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4 and 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Proportion of patients with a ≥3-point reduction in the peak pelvic pain score and a decrease in the number of standard pain relief medication
The ≥3-point reduction in the peak pelvic pain score using an 11-point numeric rating scale (NRS; scale ranging from 0 (no symptom) to 10 (extreme severity of symptom)) of the dysmenorrhea daily diary (DysDD) will be assessed and the amount of standard pain relief medication taken will be evaluated to investigate the efficacy of the study drug.
Measured: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Proportion of patients with a peak pelvic pain score of "0" or "1" and no use of standard pain relief medication
Peak pelvic pain score of "0" or "1" using an 11-point numeric rating scale (NRS; scale ranging from 0 (no symptom) to 10 (extreme severity of symptom)) of the dysmenorrhea daily diary (DysDD) and no use of standard pain relief medication during the cramping window of Cycles 3, 4, 5, and 6 will be evaluated.
Measured: At the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change of peak pelvic pain score
The peak pelvic pain score will be assessed using an 11-point numeric rating scale (NRS, scale ranging from 0 (no symptom) to 10 (extreme severity of symptom)) of the dysmenorrhea daily diary (DysDD) assessments and compared to Baseline.
Measured: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of the sum of the pelvic pain scores
The pelvic pain scores assessed during the cramping windows (4 days) of Cycles 3, 4, and 5 (i.e., 12 assessments in total) using an 11-point numeric rating scale (NRS; scale ranging from 0 (no symptom) to 10 (extreme severity of symptom)) of the dysmenorrhea daily diary (DysDD) will be summed up.
Measured: At the cramping windows of Cycles No. 3, 4 and 5 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of the change of the sum of the pelvic pain scores
The pelvic pain scores assessed during the cramping window using an 11-point numeric rating scale (NRS, scale ranging from 0 (no symptom) to 10 (extreme severity of symptom)) of the dysmenorrhea daily diary (DysDD) assessments will be summed up per cycle and compared to Baseline.
Measured: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of the change in the number of days with pelvic pain
The number of days with pelvic pain will be calculated as sum of the days with a pelvic pain above 0 on the 11-point numeric rating scale (NRS, scale ranging from 0 (no symptom) to 10 (extreme severity of symptom)) during the respective cramping window and compared to Baseline.
Measured: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the number of standard pain relief medication taken
The number of standard pain relief medication will be calculated as sum of the tablets/capsules taken during the respective cramping window and compared to Baseline.
Measured: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the number of days with use of standard pain relief medication
The number of days with use of standard pain relief medication will be calculated as sum of days with intake of standard pain relief medication during the respective cramping window and compared to Baseline.
Measured: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Proportion of patients with no use of standard pain relief medication
The number of patients who did not use any standard pain relief medication will be determined.
The analysis will be performed for all patients as well as for the subgroup of patients who took any standard pain relief medication during the cramping window of Cycle 5.
Measured: At the cramping window of Cycle No. 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the impact on the patient's daily life
The impact of pelvic pain or cramps on the patient's daily life including paid work, work around the home, or school work will be assessed on a 5-point scale being part of the dysmenorrhea daily diary (DysDD) assessments (0=not at all, 1=slightly, 2=moderately, 3=quite a bit, 4=extremely). The assessments made during each cramping window will be summed up.
The impact on physical activities, social or leisure activities, and sleep will be analyzed analogously. The missed time of paid work, work around the home, or school work will be summed up for the cramping window and tabulated by treatment group and cycle.
Measured: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Investigator's and patient's overall assessment of efficacy using a 5-point verbal rating scale
The treatment efficacy will be assessed by the investigator and the patient using a 5-point verbal rating scale with the following 5 categories: very good, good, moderate, poor, very poor.
Measured: Visits 4 (Day 85) and 5 (Day 113)
Assessment of change in the intensity of menstrual bleeding
The intensity of the menstrual bleeding will be assessed on a 5-point scale (0=no bleeding, 1=very light bleeding or spotting, 2=light bleeding, 3=moderate bleeding, 4=heavy bleeding). The assessments made during each cramping window will be summed up.
Measured: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the number of pieces of sanitary protection used
The number of pieces of sanitary protection used will be assessed on a 4-point scale (0=0, 1=1 piece, 2=2 pieces, 3=3 or more pieces). The assessments made during Day 1 to Day 3 of the cramping window will be summed up.
Measured: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the severity of nausea, vomiting, diarrhea, fatigue, weakness, fainting, and headache on a numeric rating scale (NRS)
The analysis is based on the peak NRS score of days 1, 2, and 3 per cycle (11-point NRS scale ranging from 0 (no symptom) to 10 (extreme severity of symptom)).
Measured: Change from Baseline (28 days prior to randomization) to the Days 1-3 of Cycles No. 3, 4, 5 and 6 (each cycle is 28 days).
Proportion of patients with migraine
The number of patients with migraine will be determined. The chance of patients having a migraine episode since the last clinical trial visit will be analyzed.
Measured: At Baseline (28 days prior to randomization) and Visits 0, 1, 2, 3, 4 and 5 (i.e., Days 1, 29, 57, 85, 113 and 141)
Assessment of change in the peak pelvic pain score
The change in peak pelvic pain score using an 11-point numeric rating scale (NRS, scale ranging from 0 (no symptom) to 10 (extreme severity of symptom) of the dysmenorrhea daily diary (DysDD) assessments) from cramping window of Cycle 5 to cramping window of Cycle 6 will be analyzed.
Measured: At the cramping windows of Cycles No. 5 and 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of relative change in the peak pelvic pain score
The relative change in peak pelvic pain score using an 11-point numeric rating scale (NRS, scale ranging from 0 (no symptom) to 10 (extreme severity of symptom) of the dysmenorrhea daily diary (DysDD) assessments) from cramping window of Cycle 5 to cramping window of Cycle 6 will be analyzed.
Measured: At the cramping window of Cycles No. 5 and 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the number of standard pain relief medication taken
The number of standard pain relief medication will be calculated as sum of tablets/capsules taken during the cramping window. The change from cramping window of Cycle 5 to cramping window of Cycle 6 will be analyzed.
Measured: At the cramping window of Cycles No. 5 and 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of relative change in the number of standard pain relief medication taken
The number of standard pain relief medication will be calculated as sum of tablets/capsules taken during the cramping window. The relative change from cramping window of Cycle 5 to cramping window of Cycle 6 will be analyzed.
Measured: At the cramping window of Cycles No. 5 and 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2024
- Study start12 Dec 2023
- Primary completion23 Jul 2025
- Study completion23 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary DysmenorrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, double-blind, multicenter, placebo-controlled
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 335 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bionorica SE
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- FGK Clinical Research GmbH
- Responsible party
- Sponsor
- Investigators
- Petra Stute, Prof. Dr., Principal investigator, Universitätsklinik für Frauenheilkunde, Inselspital Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06211049
- Sponsor's protocol ID
- AgnoMed
- Other IDs
- 2023-503688-41-00, U1111-1288-9484, 2023
- Status last verified
- Jul 2025
- First submitted
- 23 Nov 2023
- Last updated
- 28 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Vitex Agnus-castus BNO 1095 (20 mg) in Women With Primary Dysmenorrhea
- ClinicalTrials.gov ID
- NCT06211049
- Acronym / sponsor ID
- AgnoMed
- Conditions
- Primary Dysmenorrhea
- Keywords
- Vitex agnus-castus, Menstrual pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 335 participants (actual)
- Lead sponsor
- Bionorica SEIndustry (pharma, biotech, devices)
- Collaborators
- FGK Clinical Research GmbH
- Study start
- 12 Dec 2023 (actual)
- Primary completion
- 23 Jul 2025 (actual)
- Study completion
- 23 Jul 2025 (actual)
- First posted
- 18 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this Phase III study, the herbal product Vitex agnus-castus BNO 1095 20 mg will be tested.
The sponsor would like to find out if treatment with Vitex agnus-castus BNO 1095 20 mg may improve the cramping pain before or during menstruation (primary dysmenorrhea) (without an organic cause) in women and if this treatment is safe. It is tested, if the pelvic pain and other symptoms during menstruation improve in patients who are treated with Vitex agnus-castus BNO 1095 20 mg and if therefore the standard treatments for primary dysmenorrhea, for example pain relief medications will not have to be increased.
The study has 2 treatment groups. Patients in one group will receive Vitex agnus-castus BNO 1095 20 mg, and patients in the other group will receive a placebo. Placebo tablets look like Vitex agnus-castus BNO 1095 20 mg tablets but have no active ingredient. Patients will be randomly assigned (like tossing a coin) to one of the 2 groups (this process is called randomization). The chance for the patients to receive Vitex agnus-castus BNO 1095 is 50%. Neither the patients nor the investigators know which product the patients are taking (this method is known as "double-blind").
Detailed description
This is a randomized, placebo-controlled, double-blind, multicenter, phase III clinical trial to investigate the efficacy and safety of investigational medicinal product (IMP) Vitex agnus-castus BNO 1095 20 mg in women with primary dysmenorrhea.
The clinical trial will be conducted in Austria, Czech Republic, Germany, Hungary, Poland and Sweden.
About 390 patients will be screened so that about 300 patients (150 patients per treatment group) will be randomized.
Vitex agnus-castus BNO 1095 20 mg is extracted from the fruits of the plant Vitex agnus-castus also called monk's pepper or chaste tree. Vitex agnus-castus BNO 1095 20 mg is currently marketed for the treatment of the premenstrual syndrome (PMS) which means repeated occurrence of physical, behavioral and psychological symptoms the days before the onset of menstruation, but it is not authorized for the treatment of primary dysmenorrhea.
The study has 2 treatment groups. Patients in one group will receive Vitex agnus-castus BNO 1095 20 mg, and patients in the other group will receive a placebo. Patients will be randomly assigned 1:1 to one of the 2 groups. The chance to receive Vitex agnus-castus BNO 1095 is 50%. The study is double blinded, neither the patients nor the investigators know which product the patients are taking.
The study will last about 7 months for each patient. There will be 5 visits at the study site, and in addition the patients will receive 3 phone calls from the study site. On average, each study site visit will take about 2 hours and each phone call about half an hour.
The trial will include 3 phases: a screening and run-in phase of up to 2 menstrual cycles, a treatment phase of 4 menstrual cycles and a follow-up phase of 1 menstrual cycle. The length of each phase depends on the length of women's menstrual cycle. If their menstrual cycle is 28 days, the screening and run-in phase will take up to 59 days (slightly more than 2 menstrual cycles), the treatment phase 113 days (about 4 menstrual cycles), and the follow-up phase 28 days (1 menstrual cycle).
The main objective of this study is to determine if primary dysmenorrhea improves in women treated with Vitex agnus-castus BNO 1095 20 mg compared to placebo over a treatment duration of 3 menstrual cycles (cramping windows of Cycles 3-5).
Vitex agnus-castus BNO 1095 20 mg or placebo tablets are taken orally (means by mouth) once a day during the treatment phase.
If a patient usually takes pain relief medication for primary dysmenorrhea, the patient is allowed to continue taking this pain relief medication during study participation.
The patients will complete the dysmenorrhea daily diary (DysDD) every day in the evening. Depending on her bleeding status, the diary includes questions about menstrual bleeding, pieces of sanitary protection used, severity of the worst pain or cramps in the pelvic area on a numerical rating scale (NRS), intake of pain relief medication, and impact on daily life in an electronic diary (handheld device).
Additionally, the dysmenorrhea associated symptoms nausea, vomiting, diarrhea, fatigue, weakness, fainting, and headache will be assessed by the patients on a NRS in the electronic diary on Days 1-3 of the menstrual cycle. Migraine will be assessed by the investigator at the clinical trial visits. The patient and investigator will assess the efficacy of treatment on a 5-point verbal rating scale at the end of treatment and at the end of the study (EoS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- randomized, double-blind, multicenter, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| Vitex agnus-castus BNO 1095 (20 mg) | Experimental | Drug: Vitex agnus-castus BNO 1095 (20 mg)1 tablet once daily for about 4 menstrual cycles (cramping windows of Cycles 3-6) (i.e., 113 days in case of a 28-day menstrual cycle). |
| Placebo | Placebo comparator | Drug: Placebo1 tablet once daily for about 4 menstrual cycles (cramping windows of Cycles 3-6) (i.e., 113 days in case of a 28-day menstrual cycle). |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Women aged 18-49 years who have the capacity for consenting
- Patient has been informed of the nature, scope, and relevance of the clinical trial, voluntary agrees in participation and the trial provisions, and has duly signed the approved informed consent form (ICF)
- Diagnosed primary dysmenorrhea
- If patients take pain relief medication for primary dysmenorrhea, this medication should be taken unchanged with regard to application form and kind of medication including strength during the Screening as well as during the first three treatment cycles.
- Note: Medication (drugs) for primary dysmenorrhea as mono- or combination therapy in form of tablets/capsules regularly used by the patient before Screening is allowed to be used as standard pain relief medication during the trial apart from non-medication methods. A complete list of allowed pain relief medication is attached to the protocol.
Key exclusion criteria (26 listed)
- Non-menstruating women
- Clinically diagnosed secondary dysmenorrhea (e.g., fibroids, uterine adenomyosis, endometriosis, pelvic inflammation, ovarian pathologies, or other pelvic diseases)
- Dysmenorrhea resulting from the use of an intrauterine device
- Use of hormonal contraceptives (oral, intravaginal, transdermal, injectable, implantable), intrauterine device, or intrauterine hormone-releasing system within 6 months prior to the trial and not willing to waive it during the entire trial period
- Any surgical treatments in the past (e.g., due to myoma) that may cause pain, adhesions or scarring in the lower abdomen Note: Further diagnostic examination (e.g., laparoscopy for differential diagnosis, exclusion of endometriosis) if deemed necessary by the investigator will be outside the trial protocol and reimbursement
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitex agnus-castus BNO 1095 (20 mg)1 tablet once daily for about 4 menstrual cycles (cramping windows of Cycles 3-6) (i.e.,113 days in case of a 28-day menstrual cycle). | Drug | Vitex agnus-castus BNO 1095 (20 mg) |
| Placebo1 tablet once daily for about 4 menstrual cycles (cramping windows of Cycles 3-6) (i.e.,113 days in case of a 28-day menstrual cycle). | Drug | Placebo |
Primary outcome
Proportion of patients who respond to treatment defined as: a) a ≥3-point reduction in the peak pelvic pain score and b) no increase in the number of standard pain relief medication
Time frame: Change from Baseline (28 days prior to randomization) to the cramping window of Cycle No. 5 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Response to treatment will be determined by comparing the peak pelvic pain score (using an 11-point numeric rating scale (NRS, scale ranging from 0 (no symptom) to 10 (extreme severity of symptom) of the dysmenorrhea daily diary (DysDD) assessments) made during the cramping window of Cycle 5 with those made at Baseline and by comparing the assessments of number of tablets or capsules of standard pain relief medication taken during the cramping window of Cycle 5 with those taken at Baseline.
20 secondary outcomes
Proportion of patients who respond to treatment defined as: a) a ≥3-point reduction in the peak pelvic pain score and b) no increase in the number of standard pain relief medication in the cramping window of Cycles 3, 4, and 6 compared to Baseline
Time frame: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4 and 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Proportion of patients with a ≥3-point reduction in the peak pelvic pain score and a decrease in the number of standard pain relief medication
Time frame: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Proportion of patients with a peak pelvic pain score of "0" or "1" and no use of standard pain relief medication
Time frame: At the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change of peak pelvic pain score
Time frame: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of the sum of the pelvic pain scores
Time frame: At the cramping windows of Cycles No. 3, 4 and 5 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of the change of the sum of the pelvic pain scores
Time frame: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of the change in the number of days with pelvic pain
Time frame: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the number of standard pain relief medication taken
Time frame: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the number of days with use of standard pain relief medication
Time frame: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Proportion of patients with no use of standard pain relief medication
Time frame: At the cramping window of Cycle No. 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the impact on the patient's daily life
Time frame: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Investigator's and patient's overall assessment of efficacy using a 5-point verbal rating scale
Time frame: Visits 4 (Day 85) and 5 (Day 113)
Assessment of change in the intensity of menstrual bleeding
Time frame: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the number of pieces of sanitary protection used
Time frame: Change from Baseline (28 days prior to randomization) to the cramping windows of Cycles No. 3, 4, 5 and 6) (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the severity of nausea, vomiting, diarrhea, fatigue, weakness, fainting, and headache on a numeric rating scale (NRS)
Time frame: Change from Baseline (28 days prior to randomization) to the Days 1-3 of Cycles No. 3, 4, 5 and 6 (each cycle is 28 days).
Proportion of patients with migraine
Time frame: At Baseline (28 days prior to randomization) and Visits 0, 1, 2, 3, 4 and 5 (i.e., Days 1, 29, 57, 85, 113 and 141)
Assessment of change in the peak pelvic pain score
Time frame: At the cramping windows of Cycles No. 5 and 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of relative change in the peak pelvic pain score
Time frame: At the cramping window of Cycles No. 5 and 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of change in the number of standard pain relief medication taken
Time frame: At the cramping window of Cycles No. 5 and 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Assessment of relative change in the number of standard pain relief medication taken
Time frame: At the cramping window of Cycles No. 5 and 6 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Petra Stute, Prof. Dr. principal investigator
Universitätsklinik für Frauenheilkunde, Inselspital Bern
34 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vitex agnus-castus BNO 1095 (20 mg) in people with Primary Dysmenorrhea, run by Bionorica SE at 34 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in Germany, Czechia, Hungary, Poland, Austria and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients who respond to treatment defined as: a) a ≥3-point reduction in the peak pelvic pain score and b) no increase in the number of standard pain relief medication (time frame: Change from Baseline (28 days prior to randomization) to the cramping window of Cycle No. 5 (each cycle is 28 days). The cramping window is defined as Days -1 to 3 of a menstrual cycle (i.e., 4 days in total).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2025.