MenopausePhase 4TOTALNCT00431093
Trial to Compare the Effects of Tibolone (Livial®) and Continuous Combined Low-Dose Estradiol/Noresterone (Activelle®)
A Phase 4 study testing tibolone and low-dose estradiol/noresterone in people with Menopause, run by Organon and Co.
Trial summary
The present trial is undertaken to compare the effects of Tibolone with a low-dose HRT regimen. Read more about this study
- Who is it for?
- Ages 45 to 64 years, women only
- Conditions the study is for
- Menopause
- What is being tested?
- tibolone and low-dose estradiol/noresterone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 570 participants
- Where
- No sites listed yet
- Study dates
- Nov 2002to Mar 2005
- Phase
- Phase 4
- 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 45 to 64 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Subjects must be healthy and postmenopausal women, >= 45 and < 65 years of age, with an intact uterus.
- Subjects must have been postmenopausal for less than 15 years.
- Body Mass Index >18 and =< 32 kg/m2.
- Voluntary written informed consent is required.
Who cannot join
- Any unexplained abnormal uterine bleeding after the menopause.
- Double layer endometrial thickness = 6 mm as assessed by transvaginal ultrasonography.
- Treatment with oral estrogen and/or progestogen therapy within 4 weeks prior to screening, or treatment with transdermal therapy and local estrogen applications within 4 weeks prior to screening.
- Any previous or current unopposed estrogen administration, prior use of estrogen pellets or tamoxifen citrate (occasional use of estrogen-containing vaginal cream is allowed after the appropriate wash-out period is completed). Estrogen combined with sequential administration of progestogen should have been at least 10 days per 28 day cycle.
- The following wash-out periods apply:
- 4 weeks for transdermal hormonal treatment, local estrogen applications or other non-hormonal medication known to act on the relief of vasomotor symptoms (e.g. clonidine)
Show all 23Show fewer
- 4 weeks for phytoestrogens, tibolone, intra-uterine or oral progestogen and oral estrogen/progestogen therapy
- 6 months for progestogen implants or injections and estrogen/progestogen injectable therapy.
- Any subjects who are either using phytoestrogens, tibolone, intra-uterine or oral progestogen, progestogen implants or injections, estrogen/progestogen combination therapy or any other non-hormonal medication known to act on the relief of vasomotor symptoms and who have not observed the appropriate wash-out periods (see previous exclusion criteria).
- Any serious disease or disorder; or any endocrine disorder; (controlled hypo/hyperthyroidism and diabetes mellitus Type II is allowed).
- Diseases for which exogenous hormonal steroids are contraindicated.
- History or presence of any malignancy, except successfully treated nonmelanoma skin cancers.
- History or presence of cardiovascular or cerebrovascular conditions:
- thrombophlebitis, thrombosis or thromboembolic disorders.
- History or presence of liver, gallbladder (subjects who have had a cholecystectomy will not be excluded) or renal disease, epilepsy or classical migraine headaches.
- History or presence of clinically significant depression or other psychiatric disorders which, in the investigator's judgment, might compromise or confound the subject's participation in the trial.
- Uncontrolled high blood pressure: systolic pressure > 170 mmHg and/or diastolic pressure > 105 mmHg, measured after 5 minutes in a sitting position.
- Abnormal cervical Pap smear (corresponding to PAP = III, or LSIL, HSIL, ASCUS, AGCUS in the Bethesda classification)
- Abnormal, clinically significant results of the mammography.
- Presence of fibrocystic disease of the breast.
- Presence of otosclerosis.
- Known hypersensitivity to any of the ingredients of the trial medication.
- Any subjects using either steroids, drugs known to affect sexual functioning and mood (antidepressants, psychoactive drugs, sedatives, neuroleptics, narcotics, benzodiazepines), drugs know to interfere with the pharmacokinetics of the steroids (hydantoins, primidone, rifampicin, barbiturates, carbamazepine, griseofulvin, warfarin, ketoconazole, or products containing St. John's wort), or raloxifene hydrochloride. A wash-out period of 4 weeks will apply to subjects using these drugs. Sporadical use of benzodiazepines (twice or less a week) is allowed
About this study
Official title: A Multicenter, Randomized, Double-Blind, Double Dummy, Group-Comparative Trial to Compare the Effects of Livial® and Activelle ® on the Vaginal Bleeding Pattern, Vasomotor Complaints, Vaginal Atrophy, QoL and Sexual Function
The present trial is undertaken to compare the effects of Tibolone with a low-dose HRT regimen.
- Conditions
- Menopause
- Being tested
- tibolone, low-dose estradiol/noresterone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tiboloneDrug
Also called Livial
uncoded tablets, at a dose of 2.5 mg per tablet; Subjects were to take 1 Livialâ tablet and 1 -matched Activelleâ placebo tablet, orally, once a day (preferably at the same time).
low-dose estradiol/noresteroneDrug
Also called Activelle®
Activelleâ, estradiol (E2) 1 mg and norethisterone acetate (NETA) 0.5 mg per tablet, was supplied as uncoded tablets.
Subjects were to take 1 Activelleâ tablet and 1 Livialâ-matched placebo tablet, orally, once a day (preferably at the same time).
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | tibolone Receives: Drug: low-dose estradiol/noresterone |
| 2 | Active comparator | low-dose estradiol/noresterone Receives: Drug: tibolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
For the bleeding evaluation, subject will be given a diary card to record the days on which no bleeding, vaginal spotting or bleeding occurs
Measured: starting from baseline and during the whole trial period.
Secondary outcomes (5)
Hot flushes recorded on a daily diary card during the whole trial period.
Measured: Entire trial
A mammography to assess breast density and blood samples to determine the changes in endocrine parameters.
Measured: screening and week 48
A vaginal smear to assess the Vaginal Maturation Index and the Karyopycnotic Index results
Measured: Baseline and week 48
Urogenital complaints assessed with the Local Urogenital Complaints Rating Scale.
Measured: At baseline, week 12, week 24 and week 48
Health-related quality of life measured with the Women's Health Questionnaire 36-items (WHQ-36) the McCoy Female Sexuality Questionnaire-Short Form 9-items (MFSQ-SF) collecting prospectively medical resources utilization items
Measured: At baseline and week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2007 (estimated)
- Study startNov 2002
- Primary completionMar 2005
- Study completionMar 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MenopauseStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 570 participants (actual)
Sponsor and investigators
- Lead sponsor
- Organon and Co
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00431093
- Sponsor's protocol ID
- P06673
- Other IDs
- C-1755
- Acronym
- TOTAL
- Status last verified
- Feb 2022
- First submitted
- 2 Feb 2007
- Last updated
- 3 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Hammar ML, van de Weijer P, Franke HR, Pornel B, von Mauw EM, Nijland EA; TOTAL Study Investigators Group. Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability. BJOG. 2007 Dec;114(12):1522-9. doi: 10.1111/j.1471-0528.2007.01537.x.
PubMed 17995496
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Double Dummy, Group-Comparative Trial to Compare the Effects of Livial® and Activelle ® on the Vaginal Bleeding Pattern, Vasomotor Complaints, Vaginal Atrophy, QoL and Sexual Function
- ClinicalTrials.gov ID
- NCT00431093
- Acronym / sponsor ID
- TOTAL / P06673
- Conditions
- Menopause
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 570 participants (actual)
- Lead sponsor
- Organon and CoIndustry (pharma, biotech, devices)
- Study start
- Nov 2002
- Primary completion
- Mar 2005 (actual)
- Study completion
- Mar 2005 (actual)
- First posted
- 5 Feb 2007 (estimated)
- 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.
The present trial is undertaken to compare the effects of Tibolone with a low-dose HRT regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: low-dose estradiol/noresteronetibolone |
| 2 | Active comparator | Drug: tibolonelow-dose estradiol/noresterone |
Who may qualify
- Ages
- 45 to 64 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Subjects must be healthy and postmenopausal women, >= 45 and < 65 years of age, with an intact uterus.
- Subjects must have been postmenopausal for less than 15 years.
- Body Mass Index >18 and =< 32 kg/m2.
- Voluntary written informed consent is required.
Key exclusion criteria (23 listed)
- Any unexplained abnormal uterine bleeding after the menopause.
- Double layer endometrial thickness = 6 mm as assessed by transvaginal ultrasonography.
- Treatment with oral estrogen and/or progestogen therapy within 4 weeks prior to screening, or treatment with transdermal therapy and local estrogen applications within 4 weeks prior to screening.
- Any previous or current unopposed estrogen administration, prior use of estrogen pellets or tamoxifen citrate (occasional use of estrogen-containing vaginal cream is allowed after the appropriate wash-out period is completed). Estrogen combined with sequential administration of progestogen should have been at least 10 days per 28 day cycle.
- The following wash-out periods apply:
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 |
|---|---|---|
| tiboloneAlso: Livialuncoded tablets, at a dose of 2.5 mg per tablet; Subjects were to take 1 Livialâ tablet and 1 -matched Activelleâ placebo tablet, orally, once a day (preferably at the same time). | Drug | 2 |
| low-dose estradiol/noresteroneAlso: Activelle®Activelleâ, estradiol (E2) 1 mg and norethisterone acetate (NETA) 0.5 mg per tablet, was supplied as uncoded tablets. Subjects were to take 1 Activelleâ tablet and 1 Livialâ-matched placebo tablet, orally, once a day (preferably at the same time). | Drug | 1 |
Primary outcome
For the bleeding evaluation, subject will be given a diary card to record the days on which no bleeding, vaginal spotting or bleeding occurs
Time frame: starting from baseline and during the whole trial period.
5 secondary outcomes
Hot flushes recorded on a daily diary card during the whole trial period.
Time frame: Entire trial
A mammography to assess breast density and blood samples to determine the changes in endocrine parameters.
Time frame: screening and week 48
A vaginal smear to assess the Vaginal Maturation Index and the Karyopycnotic Index results
Time frame: Baseline and week 48
Urogenital complaints assessed with the Local Urogenital Complaints Rating Scale.
Time frame: At baseline, week 12, week 24 and week 48
Health-related quality of life measured with the Women's Health Questionnaire 36-items (WHQ-36) the McCoy Female Sexuality Questionnaire-Short Form 9-items (MFSQ-SF) collecting prospectively medical resources utilization items
Time frame: At baseline and week 48
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 3 Feb 2022.
- Derived from this study: PubMed 17995496Hammar ML, van de Weijer P, Franke HR, Pornel B, von Mauw EM, Nijland EA; TOTAL Study Investigators Group. Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability. BJOG. 2007 Dec;114(12):1522-9. doi: 10.1111/j.1471-0528.2007.01537.x.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing tibolone and low-dose estradiol/noresterone in people with Menopause, run by Organon and Co.
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 4 inclusion and 23 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 3 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
For the bleeding evaluation, subject will be given a diary card to record the days on which no bleeding, vaginal spotting or bleeding occurs (time frame: starting from baseline and during the whole trial period.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00431093, which also lists 1 linked publication.
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 3 Feb 2022.