Trial to Compare the Effects of Tibolone (Livial®) and Continuous Combined Low-Dose Estradiol/Noresterone (Activelle®) (TOTAL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00431093
First received: February 2, 2007
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

The present trial is undertaken to compare the effects of Tibolone with a low-dose HRT regimen.


Condition Intervention Phase
Menopause
Drug: tibolone
Drug: low-dose estradiol/noresterone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hot flushes recorded on a daily diary card during the whole trial period. [ Time Frame: Entire trial ] [ Designated as safety issue: No ]
  • A mammography to assess breast density and blood samples to determine the changes in endocrine parameters. [ Time Frame: screening and week 48 ] [ Designated as safety issue: No ]
  • A vaginal smear to assess the Vaginal Maturation Index and the Karyopycnotic Index results [ Time Frame: Baseline and week 48 ] [ Designated as safety issue: No ]
  • Urogenital complaints assessed with the Local Urogenital Complaints Rating Scale. [ Time Frame: At baseline, week 12, week 24 and week 48 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 570
Study Start Date: November 2002
Study Completion Date: March 2005
Primary Completion Date: March 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
tibolone
Drug: low-dose estradiol/noresterone

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).

Other Name: Activelle®
Active Comparator: 2
low-dose estradiol/noresterone
Drug: tibolone
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).
Other Name: Livial

  Eligibility

Ages Eligible for Study:   45 Years to 64 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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)
    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00431093     History of Changes
Other Study ID Numbers: P06673, C-1755
Study First Received: February 2, 2007
Last Updated: May 21, 2014
Health Authority: Belgium: National Board of Health

Additional relevant MeSH terms:
Estradiol
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Estradiol valerate
Polyestradiol phosphate
Tibolone
Anabolic Agents
Androgen Antagonists
Antihypertensive Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Cardiovascular Agents
Contraceptive Agents
Contraceptive Agents, Female
Estrogen Receptor Modulators
Estrogens
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014