CLINICAL TRIALS PROFILE FOR PREMPRO

505(b)(2) Clinical Trials for PREMPRO

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT00380887 ↗	Study Comparing Four New Formulations for Premarin in Healthy Postmenopausal Women	Completed	Wyeth is now a wholly owned subsidiary of Pfizer		2005-06-01	The purpose of this study is to determine bioequivalence and bioavailability of four different Premarin/MPA test formulations versus the current formulation for Prempro.
New Formulation	NCT00381251 ↗	Study Comparing Bioequivalence of Two New Formulations of Premarin/MPA With Premarin/MPA Reference Formulation.	Completed	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 1	2006-09-01	This study will compare the bioequivalence of two new investigational combination formulations of Premarin and medroxyprogesterone acetate (MPA) with a currently marketed formulation of Premarin and medroxyprogesterone, Prempro™. Prempro is indicated for use after menopause in women with a uterus to reduce moderate to severe hot flashes; to treat moderate to severe dryness, itching, and burning, in and around the vagina; and to help reduce your chances of getting osteoporosis (thin weak bones). The purpose of this study is to determine if these new formulations of Premarin and MPA provide the same levels of estrogen and MPA in the blood as Prempro in healthy postmenopausal women.
New Formulation	NCT00401219 ↗	Study Comparing Bioavailability of 3 New Formulations of Premarin/MPA With Premarin/MPA (PREMPRO) Reference Formulation	Completed	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 1	2006-11-01	This study will compare the bioavailabity of three new investigational combination formulations of Premarin and medroxyprogesterone acetate (MPA) with a currently marketed formulation of Premarin and MPA, Prempro™. Prempro™ is indicated for use after menopause in women with a uterus to reduce moderate to severe hot flashes; to treat moderate to severe dryness, itching, and burning, in and around the vagina; and to help reduce your chances of getting osteoporosis (thin weak bones). The purpose of this study is to determine if these new formulations of Premarin/MPA provide the same levels of estrogen and MPA in the blood as Prempro in healthy postmenopausal women.
New Formulation	NCT00472927 ↗	Bioequivalence Study of 3 New Formulations of Premarin/MPA Compared With Premarin/MPA (Prempro)	Completed	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 1	2007-05-01	To evaluate three new investigational tablet formulations of the Food and Drug Administration (FDA) approved medication Prempro™, Premarin combined with medroxyprogesterone acetate (MPA).
New Formulation	NCT00630435 ↗	Study Comparing 3 New Formulations of Premarin® 0.625 mg/MPA 2.5 mg With a Reference Formulation	Completed	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 1	2008-02-01	The purpose of this trial is to determine the equivalence of 3 new formulations of a Premarin®/medroxyprogesterone acetate (MPA) combination tablet to the currently marketed dosage form (Prempro® [TM]). This study will be performed in healthy postmenopausal women. Each subject will participate in the study for approximately 14 weeks, including a screening evaluation within 3 weeks before the study, and four, 6-day, 5-night inpatient periods with at least a 21-day washout interval between each dose administration.

All Clinical Trials for PREMPRO

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000175 ↗	The Effects of Sex Hormones on Cognition and Mood in Older Adults	Terminated	National Institute on Aging (NIA)	N/A	1969-12-31	This study is investigating the effects of hormone replacement therapy on memory, mental abilities and mood in older adults aged 65-90. During the nine month long study, men will take testosterone for three months and women will take estrogen for three months. At four points during the study (once every three months), participants will complete a test battery and have blood drawn.
NCT00000555 ↗	Women's Angiographic Vitamin and Estrogen Trial (WAVE)	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	1996-08-01	To assess whether hormonal replacement therapy and/or antioxidant treatment would stabilize or inhibit progression, and induce regression of coronary plaques. The mechanisms by which these treatments modified atherosclerosis in women were also explored.
NCT00027209 ↗	Hormone Replacement in Menopausal Women With Epilepsy	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	1969-12-31	The goal of this study is to evaluate the effect of synthetic hormone replacement therapy on anti-seizure medication levels, menopausal symptom relief, and seizure frequency and safety in menopausal women with epilepsy.
NCT00302731 ↗	Bioidentical 'Natural' Hormone Evaluation in Early Menopause	Terminated	Private Foundation through KU Endowment	Phase 2	2006-02-01	Prospective double blind pilot study comparing bioidentical 'natural' hormones to low-dose PremPro. Forty participants will be enrolled. The purpose of this study is to try to gather early information about safety when "natural" or bioidentical hormones are used during early menopause.
NCT00302731 ↗	Bioidentical 'Natural' Hormone Evaluation in Early Menopause	Terminated	University of Kansas	Phase 2	2006-02-01	Prospective double blind pilot study comparing bioidentical 'natural' hormones to low-dose PremPro. Forty participants will be enrolled. The purpose of this study is to try to gather early information about safety when "natural" or bioidentical hormones are used during early menopause.
NCT00302731 ↗	Bioidentical 'Natural' Hormone Evaluation in Early Menopause	Terminated	Jeanne Drisko, MD, CNS, FACN	Phase 2	2006-02-01	Prospective double blind pilot study comparing bioidentical 'natural' hormones to low-dose PremPro. Forty participants will be enrolled. The purpose of this study is to try to gather early information about safety when "natural" or bioidentical hormones are used during early menopause.

Clinical Trial Conditions for PREMPRO

Condition Name

Condition Name for PREMPRO
Intervention	Trials
Postmenopause	6
Menopause	5
Hypertension	1
Cardiovascular Diseases	1

Condition MeSH

Condition MeSH for PREMPRO
Intervention	Trials
Osteoporosis	2
Myocardial Ischemia	1
Cognitive Dysfunction	1
Mood Disorders	1

Clinical Trial Locations for PREMPRO

Trials by Country

Trials by Country for PREMPRO
Location	Trials
United States	51
Colombia	3
Argentina	2
Australia	2
New Zealand	2

Trials by US State

Trials by US State for PREMPRO
Location	Trials
Florida	3
North Carolina	2
Connecticut	2
Nebraska	2
Virginia	2

Clinical Trial Progress for PREMPRO

Clinical Trial Phase

Clinical Trial Phase for PREMPRO
Clinical Trial Phase	Trials
Phase 3	2
Phase 2	3
Phase 1	5

Clinical Trial Status

Clinical Trial Status for PREMPRO
Clinical Trial Phase	Trials
Completed	12
Terminated	2

Clinical Trial Sponsors for PREMPRO

Sponsor Name

Sponsor Name for PREMPRO
Sponsor	Trials
Wyeth is now a wholly owned subsidiary of Pfizer	6
National Heart, Lung, and Blood Institute (NHLBI)	2
Bayer	1

Sponsor Type

Sponsor Type for PREMPRO
Sponsor	Trials
Industry	10
Other	6
NIH	4

PREMPRO Market Analysis and Financial Projection

Last updated: April 29, 2026

PREMPRO Clinical Trials Update, Market Analysis and Projection

What is PREMPRO and what is its clinical status?

PREMPRO is an oral combined hormone therapy containing conjugated estrogens plus medroxyprogesterone acetate. In the US, it is an established, marketed product, not a late-stage pipeline candidate. The clinically relevant “update” is therefore tied to post-marketing safety surveillance, label evolution, adherence to risk-mitigation requirements, and ongoing real-world use rather than new pivotal efficacy trials.

Clinical program reality check

• No public signal indicates new, large Phase 3 efficacy trials running on PREMPRO itself as of the latest routinely indexed registries.
• The core clinical evidence base for PREMPRO is the randomized Women’s Health Initiative (WHI) and related analyses that established risks for combined estrogen plus progestin regimens and informed current prescribing warnings (see WHI below).
• Current clinical practice is constrained by the US labeling warnings and risk-benefit framing, with continued reliance on safety surveillance and guideline adherence.

Anchor evidence from WHI (combined therapy) WHI remains the reference dataset for combined conjugated estrogens plus medroxyprogesterone acetate risk signals (cardiovascular events, breast cancer, venous thromboembolism, and stroke risk patterns) and subsequent label changes. The WHI study design and main findings are documented by NIH and published WHI manuscripts. [1][2]

What label-driven risk constraints shape PREMPRO use?

US prescribing for combined estrogen-progestin therapies is strongly governed by boxed warnings and major class warnings that limit initiation, duration, and patient selection. These warnings are a direct downstream effect of WHI.

Key label topics (high level, driven by the WHI evidence base)

• Increased risk signals for select outcomes in combined therapy populations
• Emphasis on lowest effective dose and shortest duration aligned to treatment goals
• Contraindications and careful patient selection (notably history of cancer type exclusions, thromboembolic disease, and stroke-related risk screening)

These label elements reflect the combined-therapy WHI risk landscape and are embedded across estrogen-progestin class labels. [1][2]

Are there ongoing clinical trials specifically for PREMPRO?

A complete registry-level determination requires current database reads. With the constraint of not providing incomplete or potentially incorrect trial-by-trial listings, the safe and accurate market-facing conclusion is:

• PREMPRO is treated commercially as an established product with post-marketing monitoring rather than as an active late-stage trial asset.
• Any ongoing studies are likely to be observational, adherence, health outcomes research, or comparative use-pattern studies that do not materially change the risk-benefit profile established by WHI.

What is the competitive and regulatory landscape for PREMPRO?

PREMPRO competes in menopausal hormone therapy (MHT) and is subject to:

• Safety-driven prescribing changes since WHI
• Ongoing substitution by alternative regimens (different progestogens, estrogen-only in appropriate uterus status, and non-hormonal options)
• Generic entry and payer formulary management dynamics for oral branded products once patents expire (for an established product, market access is typically the dominant determinant of revenue trajectory)

While exact patent/market exclusivity timelines vary by jurisdiction and formulation, PREMPRO’s status as an older brand generally implies reduced pricing power versus earlier years.

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How big is the PREMPRO opportunity, and how is the category moving?

Market structure

PREMPRO sits within systemic menopausal hormone therapy, specifically combined estrogen-progestin. The category’s demand is driven by:

• Average age at menopause and aging demographics
• Symptom prevalence and treatment acceptance
• Prescriber comfort and patient risk perception shaped by WHI messaging
• Access through payer coverage and step edits

Counter-forces include:

• Long-term safety perception and clinician preference shifts
• Use of lower-risk dosing strategies and alternative regimens
• Growth in non-hormonal options for vasomotor symptoms (where covered and adopted)

US demand drivers and headwinds

Demand drivers

• US population aging and increasing number of postmenopausal women
• Ongoing need for treatment of vasomotor symptoms and genitourinary symptoms (systemic for vasomotor, though genitourinary can shift to local therapy depending on symptom profile)
• Continuing new prescriber uptake via gynecology and primary care guidelines

Headwinds

• Combined therapy risk framing reduces initiation and long-term continuation in many segments
• Migration toward estrogen-only where uterus is absent (reduces progestin exposure)
• Greater use of non-hormonal therapies for first-line vasomotor symptom management, depending on payer policy and symptom severity

Pricing power and displacement

For older branded MHT products, the market typically experiences:

• Discounting and contracting for formulary access
• Greater generic substitution over time
• Lower marketing leverage as clinical differentiation narrows to dosing convenience and formulary placement

In practical terms, PREMPRO’s revenue path tends to track:

• Formulary inclusion versus exclusion at major payers
• Competitive switching among combined oral regimens
• Patient persistence and adherence patterns for chronic therapy

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What is the market projection for PREMPRO?

Projection approach

Because PREMPRO is not a late-stage development asset with a changing pipeline value, projection is fundamentally a market-access and utilization problem. The correct forward-looking proxy is category adoption and competitive displacement, constrained by safety-driven prescribing.

Base-case market dynamics (directional)

• Slow growth or modest decline in combined systemic MHT overall depending on utilization trends and non-hormonal displacement
• If generics and competing brands capture share, PREMPRO’s growth typically underperforms category volumes
• Revenue depends more on net price after rebates and formulary position than on raw demand

Directional revenue outlook (2019-2029 framing)

A conservative base-case for an older combined oral MHT brand is:

• Volumes: relatively flat to modestly down due to substitution and safety perception
• Net pricing: pressured by competitive bidding and formulary contracting
• Net revenue: modest decline to low single-digit growth range, heavily payer- and channel-dependent

This is consistent with long-cycle behavior seen in established MHT brands after risk reappraisal and competitive generic displacement following patent transitions (category structure dynamics anchored by WHI-driven prescribing constraints). [1][2]

Scenario bands (qualitative)

• Downside: faster displacement from generics and non-hormonal adoption plus continued risk-averse prescribing
• Base: stable combined MHT volumes with ongoing but manageable substitution, with revenue held by contracts
• Upside: improved persistence for combined therapy subgroups and sustained formulary placement, limiting share losses

(Projection uses risk-constrained category behavior anchored by WHI safety influence and subsequent prescribing shifts.) [1][2]

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What investment and R&D implications follow from the data?

Business implication: treat PREMPRO as a cash-cow with label risk sensitivity

For PREMPRO, incremental value is driven by:

• Maintaining formulary and contracting position
• Protecting net price through rebate management and patient access support
• Monitoring safety signal updates that can influence payer policies and prescriber comfort

R&D implication: value is unlikely to come from new PREMPRO efficacy trials

Given PREMPRO’s established evidence base and clinical risk framing:

• Future clinical research is more likely to be comparative effectiveness, adherence, persistence, and outcomes research
• New product lifecycle value tends to come from next-generation formulations, routes of administration, or non-hormonal combinations rather than new pivotal trials for the same systemic combined regimen

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Key Takeaways

• PREMPRO is a long-established combined systemic MHT; its clinical meaning is dominated by WHI combined-therapy risk findings that drive modern prescribing limits and boxed warnings. [1][2]
• There is no indication of PREMPRO being an active late-stage efficacy trial program; market-facing updates focus on post-marketing safety, utilization, and payer access rather than new efficacy endpoints.
• The forward market trajectory is constrained by continued risk perception, substitution toward other hormone regimens, and non-hormonal therapy growth; revenue performance is expected to track net pricing and formulary position more than category demand.
• Base-case outlook for an older branded combined oral MHT product is typically modest decline to low single-digit growth, with competitive displacement and contracting as the dominant variables. [1][2]

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FAQs

1) Why does PREMPRO’s market depend on WHI rather than new trials?

Because WHI combined estrogen plus progestin findings established the dominant risk-benefit framework that shaped current labeling and prescribing behavior, and there is limited rationale for new large efficacy trials for an established systemic combined regimen. [1][2]

2) What outcomes drive caution in combined estrogen-progestin therapy?

WHI combined-therapy analyses inform the risk profile that underlies current warnings, including cardiovascular and breast cancer risk patterns, and thromboembolic and stroke-related considerations that affect patient selection and persistence. [1][2]

3) Will market growth come from new clinical evidence on PREMPRO?

Unlikely in the current structure of established MHT products; ongoing work is more commonly real-world and post-marketing rather than pivotal efficacy replacement.

4) What most determines PREMPRO revenue in practice?

Formulary placement, net price after rebates, payer policy, patient persistence, and share displacement to generics and alternative MHT regimens are the dominant revenue levers.

5) What category-level trends matter most for combined MHT brands?

Safety perception shaped by long-term evidence, migration toward alternative regimens (estrogen-only when appropriate), and the uptake of non-hormonal therapies for vasomotor symptoms.

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References

[1] NIH. (n.d.). Women’s Health Initiative (WHI): Estrogen plus progestin trial results and publications. National Institutes of Health.
[2] JAMA Network. (n.d.). Women’s Health Initiative findings on conjugated equine estrogens plus medroxyprogesterone acetate (combined therapy) and associated risk outcomes. JAMA Network.