Dehydroepiandrosterone (DHEA) + Acolbifene Against Vasomotor Symptoms (Hot Flushes) in Postmenopausal Women

• Co-primary endpoint: change from baseline to week 12 in frequency of moderate to severe hot flushes. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Co-primary endpoint: change from baseline to week 12 in severity of moderate to severe hot flushes. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

• Change from baseline to week 12 on vaginal atrophy parameters (superficial cells, parabasal cells, pH, vaginal atrophy symptoms). [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline to week 12 on sexual function and quality of life as evaluated by appropriate questionnaires. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Tolerance to systemic administration of DHEA and acolbifene. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

The purpose of this Phase III trial is to evaluate the efficacy of oral administration of dehydroepiandrosterone (DHEA) combined with acolbifene (a selective estrogen receptor modulator (SERM)) on vasomotor symptoms (hot flushes) in postmenopausal women.

• Vasomotor Symptoms
• Hot Flushes

• Drug: Placebo
  Placebo DHEA capsules (2) + placebo acolbifene capsule (1); daily oral dosing for 12 weeks.
• Drug: DHEA and Acolbifene
  DHEA capsules (2 x 50 mg) + acolbifene capsule (1 x 20 mg); daily oral dosing for 12 weeks.
  Other Name: Prasterone; dehydroepiandrosterone; EM-652.HCl

• Placebo Comparator: Control (placebo)
  Intervention: Drug: Placebo
• Experimental: DHEA + Acolbifene
  Intervention: Drug: DHEA and Acolbifene

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Main Inclusion Criteria:

• Postmenopausal women (non-hysterectomized or hysterectomized).
• Women between 40 and 75 years of age.
• Willing to participate in the study and sign an informed consent.
• Women having many moderate to severe hot flushes.
• For non-hysterectomized women, willing to have an endometrial biopsy at baseline and end of-study.

Main Exclusion Criteria:

• Undiagnosed abnormal genital bleeding.
• Hypertension equal to or above 140/90 mm Hg.
• The administration of any investigational drug within 30 days of screening visit.
• Endometrial hyperplasia (simple or complex hyperplasia with or without atypia), cancer or endometrial histology showing proliferative, secretory or menstrual type characteristics at histologic evaluation of endometrial biopsy performed at screening.