CLINICAL TRIALS PROFILE FOR PROGESTERONE

505(b)(2) Clinical Trials for PROGESTERONE

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 Dosage	NCT01300351 ↗	Comparing the Efficacy and Tolerability of Fulvestrant 500 mg Versus 250 mg in Advanced Breast Cancer Women	Completed	AstraZeneca	Phase 3	2011-03-01	The purpose of this study is to evaluate the efficacy of a new dose of 500mg Fulvestrant with the standard dose of 250mg in Chinese postmenopausal women with oestrogen receptor positive advanced breast cancer who have failed a prior endocrine treatment.
OTC	NCT01786252 ↗	Effect of hCG on Receptivity of the Human Endometrium	Completed	Michigan State University	Phase 4	2013-01-01	Worldwide, 1 in 12 couples experience difficulty in getting pregnant and seek the help of assisted reproductive technologies (ART) such as in vitro fertilization (IVF-egg is fertilized by sperm outside the body), ovarian stimulation (medications are used to stimulate egg development) and intra-cytoplasmic injection (ICSI-single sperm is injected directly into the egg). Regardless of the ART procedure being performed, the newly fertilized embryo must still implant into the mothers endometrium (inner lining of uterus). This implantation process in humans is surprisingly inefficient and accounts for up to 50% of ART failures. Intrauterine infusion of hCG prior to embryo transfer has recently been shown to increase pregnancy rates but the cellular mechanism for this increase is unknown. Successful implantation requires the newly fertilized embryo and the endometrium develop in a synchronized manner. This coordinated development is accomplished, in part, by proteins secreted by the embryo which circulate throughout the maternal bloodstream and alert the maternal body organs (i.e. ovary, endometrium, breast, ect) that fertilization has occurred. One of the earliest of these secreted proteins is human chorionic gonadotropin (hCG), which is the molecule detected in over-the-counter pregnancy tests. From previous studies, we know that hCG production by the embryo alerts the ovary to continue producing progesterone, a hormone required for pregnancy. However, very little is known about the direct effect of hCG on the endometrium during early pregnancy in humans. Using animal models, hCG has been shown to induce specific changes in the endometrium, suggesting that embryo-derived hCG may be "priming" the endometrium in anticipation of implantation. The goal of this research study is to examine the direct effect of hCG on the human endometrium and see if this "priming effect" is also present in humans. Findings from this research may reveal whether pre-treatment with hCG can enhance ART outcomes, especially pregnancy rates.
New Combination	NCT04296942 ↗	BN-Brachyury, Entinostat, Adotrastuzumab Emtansine and M7824 in Advanced Stage Breast Cancer (BrEAsT)	Completed	National Cancer Institute (NCI)	Phase 1	2021-05-04	Background: Breast cancer is the second most common cause of U.S. cancer deaths in women. Immunotherapy drugs use a person s immune system to fight cancer. Researchers want to see if a new combination of immunotherapy drugs can help treat breast cancer that has gone to places in the body outside of the breast (metastasized). Objective: To learn if a new combination of immunotherapy drugs can shrink tumors in people with metastatic breast cancer. Eligibility: Adults 18 and older who have been diagnosed with metastatic breast cancer, such as Triple Negative Breast Cancer (TNBC) or ER-/PR-/HER2+ Breast Cancer (HER2+BC) Design: Participants will be screened with: medical history physical exam disease confirmation (or tumor biopsy) tumor scans (computed tomography, magnetic resonance imaging, and/or bone scan) blood and urine tests electrocardiogram (measures the heart s electrical activity) echocardiogram (creates images of the heart). Participants will be assigned to 1 of 3 groups. The drugs they get will be based on the group they are in. Drugs are given in cycles. Each cycle = 3 weeks. Participants will be seen in clinic every 3 weeks, prior to the start of a new cycle. At each visit, participants will have an clinical exam, have blood drawn and will be asked about any side effects. They will repeat the screening tests during the study. New scans, like a CT scan, will be done every 6 weeks to see if the treatment is working. All participants will get BN-Brachyury. It is 2 different vaccines - a prime and a boost. First the priming vaccines, called MVA-BN-Brachyury help to jump start the immune system. Next the boosting vaccines, called FPV-Brachyury help to keep the immune system going. They are injected under the skin during different cycles. All participants will get M7824 (also known as Bintrafusp alfa ), which is an immunotherapy drug. Some participants will get a commonly used drug is HER2+ breast cancer called adotrastuzumab emtansine (also known as T-DM1DM1 or kadcyla). For both, a needle is inserted into a vein to give the drugs slowly. Some participants will take Entinostat weekly by mouth. It is in tablet form. Participants will keep a pill diary. Participants will continue on their assigned treatment until their cancer grows, they develop side effects or want to stop treatment. About 28 days after treatment ends, participants will have a follow-up visit or a telephone call. Then they will be contacted every 3 months for 1 year, then every 6 months for 1 year. They may have more tumor scans or continue treatment.
New Formulation	NCT05899010 ↗	MIcronized PROgesterone in Frozen Embryo Transfer Cycles	Not yet recruiting	Fundación Santiago Dexeus Font	Phase 3	2023-06-01	This randomized trial was designed as non-inferiority trial aiming to compare ongoing pregnancy rates following LPS with 600 mg/day vs 800 mg/day vaginal VMP. All patients will undergo an artificial cycle frozen embryo transfer (AC-FET) with transdermal estradiol 6mg/day Patients undergoing an artificial cycle FET will start estrogen priming with transdermal estradiol 6mg/day (Estrogel®) on cycle D1-D3. Following 10-12 days of estrogen priming, patients will be randomized to luteal phase support with a standard formulation (200mg tid, Utrogestan®) or a new formulation (400mg bid) VMP. All patients will undergo a serum P measurement on the day before embryo transfer (ET). Patients with P

All Clinical Trials for PROGESTERONE

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.
NCT00000176 ↗	Alzheimer's Disease Prevention Trial	Completed	National Institute on Aging (NIA)	Phase 3	1969-12-31	This is a three-year study to determine if estrogens can prevent memory loss and Alzheimer's disease in women with a family history of Alzheimer's disease.
NCT00000295 ↗	Progesterone Treatment in Female Smokers - 12	Completed	University of Minnesota	Phase 2	1999-04-01	The purpose of this study is to investigate progesterone effects in female smokers
NCT00000295 ↗	Progesterone Treatment in Female Smokers - 12	Completed	University of Minnesota - Clinical and Translational Science Institute	Phase 2	1999-04-01	The purpose of this study is to investigate progesterone effects in female smokers

Clinical Trial Conditions for PROGESTERONE

Condition Name

Condition Name for PROGESTERONE
Intervention	Trials
Breast Cancer	168
Infertility	145
Polycystic Ovary Syndrome	44
Menopause	29

Condition MeSH

Condition MeSH for PROGESTERONE
Intervention	Trials
Breast Neoplasms	297
Infertility	198
Premature Birth	71
Polycystic Ovary Syndrome	65

Clinical Trial Locations for PROGESTERONE

Trials by Country

Trials by Country for PROGESTERONE
Location	Trials
United Kingdom	92
France	52
Germany	52
Belgium	49
Japan	46

Trials by US State

Trials by US State for PROGESTERONE
Location	Trials
California	132
New York	108
Texas	104
North Carolina	87
Florida	85

Clinical Trial Progress for PROGESTERONE

Clinical Trial Phase

Clinical Trial Phase for PROGESTERONE
Clinical Trial Phase	Trials
PHASE4	10
PHASE3	17
PHASE2	22

Clinical Trial Status

Clinical Trial Status for PROGESTERONE
Clinical Trial Phase	Trials
Completed	529
Recruiting	212
Unknown status	143

Clinical Trial Sponsors for PROGESTERONE

Sponsor Name

Sponsor Name for PROGESTERONE
Sponsor	Trials
National Cancer Institute (NCI)	121
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	48
Cairo University	27

Sponsor Type

Sponsor Type for PROGESTERONE
Sponsor	Trials
Other	1522
Industry	343
NIH	255

Progesterone Clinical Trials Update, Market Analysis, and Market Projection (US and Global)

Last updated: May 20, 2026

Progesterone is the active ingredient in multiple branded and generic hormone therapies across obstetrics, infertility, and women’s health, with products marketed as oral capsules, vaginal gels/inserts, and injectable formulations. Clinical development is fragmented by formulation (API plus delivery system), route (oral versus vaginal versus IM), and indication (luteal support, threatened miscarriage, IVF support, hormone replacement). Market projection is driven by (1) procedural IVF volumes, (2) use of progesterone for luteal phase support and early pregnancy bleeding protocols, (3) uptake of lower-burden regimens (vaginal products with simplified dosing or sustained release), and (4) patent and exclusivity coverage that is generally product-specific rather than API-wide.

What is the latest clinical trials landscape for progesterone (2024–2026)?

The progesterone clinical trials ecosystem is dominated by formulation and route optimization rather than discovery of new molecular entities. Trial activity clusters in reproductive endocrinology and obstetrics: luteal phase support for IVF/ART, prevention/treatment of threatened miscarriage, and hormone replacement therapy add-on regimens.

Which progesterone formulations are seeing the most clinical activity?

Across public registries and conference disclosures, development concentrates in:

• Vaginal progesterone (gels/creams/inserts) for luteal support and pregnancy bleeding indications
• Oral progesterone (capsules/softgels) where tolerability and adherence drive adoption
• Injectable progesterone (IM) where supply reliability and clinician preference support sustained use
• Sustained-release or modified-release designs intended to reduce dosing frequency and improve steady exposure in early pregnancy and IVF protocols

What endpoints are most common in progesterone trials?

Trials typically measure:

• Clinical pregnancy rate and ongoing pregnancy
• Miscarriage/early pregnancy loss rates
• Time-to-bleeding resolution for threatened miscarriage settings
• Pharmacokinetics (Cmax, Tmax, AUC) for formulation comparisons
• Safety metrics: adverse events, endometrial effects (for HRT contexts), and maternal-fetal outcomes where applicable

How are recent trends shaping trial design?

• Route-specific comparative trials (vaginal versus oral, or different vaginal products) focus on PK similarity plus clinical endpoints in fertility workflows.
• Protocol-driven use: trials increasingly reflect evolving guideline language for luteal support and threatened miscarriage management.
• Safety surveillance is standard given progesterone’s established therapeutic use.

Which progesterone indications are driving trials and registrations right now?

Progesterone’s most active trial themes follow recurring care pathways.

Is progesterone still targeting IVF luteal phase support?

Yes. IVF/ART remains a consistent driver because luteal support is routine and protocol variation creates room for product-level optimization:

• Vaginal progesterone regimens are compared for pregnancy outcomes and tolerability.
• Oral progesterone regimens are tested for convenience and adherence.
• PK bridging is frequently used where clinical endpoint studies are costly.

Are trials continuing in threatened miscarriage and early pregnancy bleeding?

Yes. Progesterone is studied for early pregnancy bleeding and threatened miscarriage, usually with endpoints tied to bleeding resolution and pregnancy maintenance. Where local practice varies, trials are also used to generate data aligned to national protocols and guideline committees.

What about progesterone in hormone replacement therapy?

HRT is generally less dynamic clinically, but formulation improvements and regimen simplification can still support localized studies, especially for postmenopausal patients where adherence matters.

How big is the progesterone market today and what’s the revenue mix by route?

Progesterone market size is difficult to summarize as a single number because “progesterone” sales split across:

• multiple brand names and company-specific products
• generic substitution
• distinct route categories (oral, vaginal, injectable)
• indication-driven prescribing (fertility clinics versus obstetrics)

In practice, market revenues concentrate where dosing adherence is critical and where clinical protocols standardize use:

• Vaginal products: typically capture substantial shares in IVF/ART and pregnancy bleeding workflows due to established clinician familiarity and dosing practices.
• Oral capsules/softgels: supported by adherence and outpatient convenience.
• Injectables: retained in some settings where supply chains, cost, and prescriber preferences sustain use.

What market factors determine progesterone growth over the next 5 years?

1) IVF/ART volume and expansion

Even modest growth in ART volumes increases demand for luteal support. Countries with rising fertility treatment uptake, plus clinic-level protocol standardization, support steady utilization.

2) Guideline adherence and protocol standardization

When national and specialty guidelines specify progesterone regimens for luteal support or threatened miscarriage, prescribing becomes repeatable and less substitutable at the clinical protocol level. This shifts competition toward product tolerability, dosing simplicity, and formulary position.

3) Generic entry and price pressure

Progesterone experiences heavy generic substitution in many markets. Price erosion can be rapid once product-specific exclusivity expires. This creates a split market:

• Branded or protected formulations with better gross-to-net and formulary retention
• Generic-heavy segments where volume still grows but margins compress

4) Formulation differentiation

Route and formulation differences drive competitive positioning:

• reduced dosing frequency
• better patient adherence
• improved tolerability
• stability and ease-of-use in clinic and home settings

When does progesterone lose exclusivity, and what patents matter (product-specific rather than API-wide)?

Exclusivity timing depends on each product’s patent and regulatory status. For progesterone, the API is long off discovery stage. Patent estates are typically tied to:

• specific formulations (e.g., composition and/or excipient systems)
• dosage forms (vaginal insert/gel configurations, capsule strengths)
• manufacturing methods
• therapeutic regimens or method-of-use claims tied to particular clinical contexts

What is the Orange Book status for progesterone products?

Orange Book listing status is product-specific. In progesterone, generic entry risk usually appears at the level of:

• ANDA approvals for specific dosage forms/strengths
• Paragraph IV challenges tied to formulation-specific patents or listed method-of-use patents

A complete, accurate Orange Book matrix requires product name and strength; “progesterone” is not a single Orange Book entry.

What generic entry risks exist for progesterone formulations?

Generic entry risk depends on whether the innovator holds any remaining:

• listed formulation patents in Orange Book for the specific dosage form
• listed method-of-use patents that are still active
• pediatric exclusivity or other regulatory exclusivities attached to a particular branded product

In markets where progesterone has matured and multiple generics exist, new generic entries tend to focus on:

• under-served strengths or routes
• biosimilar-like dynamics do not apply (progesterone is a small molecule)
• market opportunities created by supply disruptions, formulary gaps, or higher convenience products

How does progesterone compare with dydrogesterone and other progestins?

Progesterone is often compared commercially and clinically against:

• dydrogesterone (different receptor profile and marketed regimens in some markets)
• medroxyprogesterone acetate (HRT contexts, endometrial protection use patterns)
• other progestins used in specific gynecologic workflows

Commercial impact depends on:

• guideline preference in local markets
• clinician familiarity
• insurance coverage and formulary placement
• evidence base for threatened miscarriage and IVF support outcomes under local standards

What patent litigation affects progesterone generics (US)?

Progesterone litigation is generally product-patent specific, often focusing on:

• whether generic products infringe formulation or method-of-use claims
• Orange Book listing validity and enforceability
• settlement-triggered launch timing

A comprehensive litigation update requires product-specific identifiers and docket-level tracking; there is no single “progesterone patent estate” because competition and disputes are organized around dosage forms and company products.

Market projection: baseline scenario for progesterone (5-year outlook)

Given the lack of a single consolidated “progesterone” product and the intensity of generic substitution, market projection should be interpreted as a function of route mix and regulation of branded differentiation rather than as an API-wide monolith.

Baseline growth drivers

• steady ART volumes and protocol adoption in multiple geographies
• ongoing use of progesterone for early pregnancy bleeding under standard of care
• incremental uptake of convenience-favoring formulations (route- and dosing-specific)

Baseline headwinds

• generic price compression across oral and injectable segments where patents expire and multiple ANDAs exist
• formulary tightening under payer cost controls
• competitive intensity from multiple manufacturers for the same dosage forms

Projection structure used by industry

• Volume growth modest to moderate, tied to fertility clinic utilization and obstetrics protocols
• Value growth constrained by generic price erosion
• Outperformance for companies with differentiated dosing or protected formulation-specific niches

Commercial outlook by route (directional)

Vaginal progesterone

• Typically more resilient clinically because protocols are embedded in fertility workflows and pregnancy bleeding care pathways.
• Competitive pressure exists from generics, but route familiarity and dosing adherence keep stable demand.

Oral progesterone

• Convenience supports demand, but oral segments face aggressive generic competition and price pressure.
• Differentiation is more likely to be driven by patient experience and formulation convenience than by clinical superiority.

Injectable progesterone

• Demand is tied to clinical preference and supply continuity.
• Price erosion can be significant where multiple generics exist and where procurement contracts consolidate.

What should investors and BD teams monitor next for progesterone?

Key near-term indicators for business decisions:

• FDA labeling changes that affect route preference (safety communication and pregnancy-related labeling updates)
• ANDA approval pace for key strengths and dosage forms
• settlement announcements that shift launch timelines
• reimbursement changes affecting IVF/ART cycle coverage and obstetric pathways
• manufacturing and supply chain stability for high-volume dosage forms

Key Takeaways

• Progesterone development is product- and route-specific, with the bulk of clinical activity focused on vaginal/oral delivery optimization in IVF/ART and threatened miscarriage workflows.
• Market growth is volume-led (fertility and obstetrics protocols) and value-constrained by generic price compression.
• Patent and exclusivity risk is not “API-wide”; it is tied to formulation, dosage form, and method-of-use claims for specific branded products.
• The 5-year outlook is best treated as a split between generics (margin pressure) and differentiated or protected formulations (higher pricing power within their niches).

FAQs

1. How do vaginal progesterone inserts and gels differ in clinical outcomes for IVF luteal support?
2. What FDA exclusivities or listed patents typically block ANDA launches for branded progesterone products?
3. Which progesterone dosage forms are most exposed to rapid generic substitution in the US?
4. How do progesterone and dydrogesterone adoption patterns vary across US versus EU markets?
5. What trial endpoints matter most for progesterone in threatened miscarriage to support labeling changes?

References

1. FDA. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. (Accessed via FDA Orange Book database).
2. ClinicalTrials.gov. Search results for “progesterone” and condition filters for infertility/IVF and threatened miscarriage. (Accessed via ClinicalTrials.gov database).
3. FDA. Drugs@FDA: FDA-approved drug products and approvals. (Accessed via Drugs@FDA database).