385 Participants Needed

Bazedoxifene + Estrogens for Atherosclerosis

(APPT Trial)

JT
LM
Overseen ByLora Maxwell, RN
Age: 18 - 65
Sex: Female
Trial Phase: Phase 2
Sponsor: University of Southern California
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

Advancing Postmenopausal Preventive Therapy (APPT) is a randomized, double-blinded, placebo-controlled trial designed to determine the effects of tissue selective estrogen complex (TSEC) therapy on the progression of subclinical atherosclerosis and cognitive decline in 360 healthy postmenopausal women.

Will I have to stop taking my current medications?

The trial requires that you stop using postmenopausal hormone replacement therapy (HRT) at least 1 month before joining. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Bazedoxifene + Estrogens for Atherosclerosis?

Research on postmenopausal monkeys shows that Bazedoxifene combined with conjugated estrogens may help reduce atherosclerosis (buildup of fats and cholesterol in artery walls) in coronary, peripheral, and cerebral arteries. Additionally, studies in postmenopausal women indicate that this combination can positively affect lipid levels, which are related to heart health.12345

Is the combination of bazedoxifene and conjugated estrogens safe for humans?

The combination of bazedoxifene and conjugated estrogens has been shown to be generally safe in humans, with studies indicating it does not stimulate breast or uterine tissues. However, there may be an increased risk of hot flushes, leg cramps, and blood clots compared to a placebo.16789

How is the drug Bazedoxifene + Estrogens unique for treating atherosclerosis?

Bazedoxifene combined with conjugated estrogens is unique because it is a new class of therapy that pairs a selective estrogen receptor modulator with estrogens, potentially offering benefits for atherosclerosis by affecting lipid metabolism without stimulating breast or endometrial tissue.124710

Research Team

HN

Howard N. Hodis, MD

Principal Investigator

University of Southern California Atherosclerosis Research Unit

Eligibility Criteria

This trial is for healthy postmenopausal women aged 45-59, within six years of menopause and with low estrogen levels. It's not for those who've had a hysterectomy, cardiovascular disease, diabetes, severe illness with short prognosis, liver disease, blood clots in veins or lungs, breast cancer history or recent hormone therapy.

Inclusion Criteria

I am a woman aged 45-59, less than 6 years postmenopausal, with low estrogen levels.

Exclusion Criteria

I have a history of heart problems.
Your blood test shows that you have high levels of creatinine, which is a waste product in the blood.
I have been using hormone replacement therapy for the past month.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Bazedoxifene/Conjugated Equine Estrogen or placebo for up to 3 years

Up to 3 years
Visits at baseline, 6 months, 1 year, 1.5 years, 2 years, 2.5 years, and 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

  • Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg
  • Placebo
Trial OverviewThe APPT study tests if a combo pill (bazedoxifene and conjugated estrogens) can slow down heart artery hardening and mental decline compared to a placebo. The trial randomly assigns participants to either the treatment or placebo group in secret.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: BZA/CEExperimental Treatment1 Intervention
Oral bazedoxifene 20 mg / conjugated estrogens 0.45 mg
Group II: PlaceboPlacebo Group1 Intervention
Oral matching placebo

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials
956
Recruited
1,609,000+

National Institute on Aging (NIA)

Collaborator

Trials
1,841
Recruited
28,150,000+

Findings from Research

Bazedoxifene demonstrated linear pharmacokinetics in healthy postmenopausal women, with steady-state achieved in one week and no unexpected accumulation across doses of 5 to 40 mg.
The drug was found to be safe and well tolerated, with an estimated oral bioavailability of approximately 6%, indicating that it is effectively absorbed in the body.
Pharmacokinetics, Dose Proportionality, and Bioavailability of Bazedoxifene in Healthy Postmenopausal Women.McKeand, W.[2018]
A pooled analysis of five phase-3 trials involving 4868 healthy, non-hysterectomized postmenopausal women showed that conjugated estrogens/bazedoxifene (CE/BZA) has an acceptable cardiovascular safety profile, with low rates of venous thromboembolic events (VTEs) and comparable rates of stroke and coronary heart disease (CHD) to placebo.
The incidence of VTEs was very low across different doses of CE/BZA, with rates of 0.3 to 0.7 per 1000 woman-years, indicating that CE/BZA is a safe option for managing menopausal symptoms without significantly increasing cardiovascular risks.
Cardiovascular safety of conjugated estrogens plus bazedoxifene: meta-analysis of the SMART trials.Komm, BS., Thompson, JR., Mirkin, S.[2015]
Bazedoxifene acetate is an investigational oral drug that effectively prevents bone loss and reduces vertebral fracture risk in postmenopausal women, without affecting the endometrium or breast tissue.
When combined with conjugated estrogens, bazedoxifene shows promise in improving menopausal symptoms while providing skeletal benefits, making it a potential treatment for postmenopausal osteoporosis and related symptoms.
Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis.Lewiecki, EM.[2019]

References

Effects of bazedoxifene alone and with conjugated equine estrogens on coronary and peripheral artery atherosclerosis in postmenopausal monkeys. [2022]
Effects of bazedoxifene, conjugated equine estrogens, and a tissue-selective estrogen complex containing both bazedoxifene and conjugated equine estrogens on cerebral artery atherosclerosis in postmenopausal monkeys. [2021]
Effects of conjugated estrogens/bazedoxifene on lipid and coagulation variables: a randomized placebo- and active-controlled trial. [2015]
Pharmacokinetics, Dose Proportionality, and Bioavailability of Bazedoxifene in Healthy Postmenopausal Women. [2018]
Relief of vasomotor symptoms with the tissue-selective estrogen complex containing bazedoxifene/conjugated estrogens: a randomized, controlled trial. [2015]
Cardiovascular safety of conjugated estrogens plus bazedoxifene: meta-analysis of the SMART trials. [2015]
Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis. [2019]
Efficacy and safety of bazedoxifene in postmenopausal Asian women. [2022]
Efficacy and safety of bazedoxifene for postmenopausal osteoporosis. [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
A double-blind, randomized, ascending, multiple-dose study of bazedoxifene in healthy postmenopausal women. [2018]