NCT03199963 (4WARD) is a Phase 3 clinical trial of 4-OH tamoxifen in Mammographic Breast Density, sponsored by BHR Pharma, LLC.

Who is sponsoring NCT03199963?

NCT03199963 is sponsored by BHR Pharma, LLC.

What drugs are being tested in NCT03199963?

Interventions in NCT03199963: 4-OH tamoxifen, Placebo.

What condition does NCT03199963 study?

NCT03199963 studies Mammographic Breast Density.

Is NCT03199963 still recruiting?

NCT03199963 is currently terminated. Last updated 26 July 2022.

Are results published for NCT03199963?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2022-07-26 · How we verify

NCT03199963: 4WARD

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

Trial of 4-Hydroxytamoxifen (4-OHT) Gel in Women Aimed at Reducing Dense Breast Tissue

Terminated Phase 3 Results posted Last updated 26 July 2022

What this trial tests

Phase 3 trial testing 4-OH tamoxifen in Mammographic Breast Density in 223 participants. Terminated before completion.

Timeline

21 August 2017

Primary endpoint
14 January 2019

23 April 2019

Quick facts

Lead sponsor	BHR Pharma, LLC
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	223
Start date	21 August 2017
Primary completion	14 January 2019
Estimated completion	23 April 2019
Sites	19 locations across United States, Germany, Spain

Drugs / interventions tested

4-OH tamoxifen — full drug profile →
Placebo

Conditions studied

Mammographic Breast Density — all drugs for Mammographic Breast Density →

Sponsor

BHR Pharma, LLC — full company profile →

Who can join

Adults 35 to 75, female only, with Mammographic Breast Density. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number and Severity of Adverse Events (AEs) Secondary · Blinded Phase: Baseline; Weeks 13, 26, 39, 52/EOS and Open Label Phase

AEs monitored and reported throughout study

Subjects with at least one mild AE

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel) in Blinded Phase	56
Matching Placebo Gel in Blinded Phase	31
Open Label BHR-700 (0.2% 4-OHT Gel) Following BHR-700 in Blinded Phase	2
Open Label BHR-700 (0.2% 4-OHT Gel) Following Placebo in Blinded Phase	1

Subjects with at least one moderate AE

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel) in Blinded Phase	49
Matching Placebo Gel in Blinded Phase	29
Open Label BHR-700 (0.2% 4-OHT Gel) Following BHR-700 in Blinded Phase	2
Open Label BHR-700 (0.2% 4-OHT Gel) Following Placebo in Blinded Phase	1

Subjects with at least one severe AE

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel) in Blinded Phase	8
Matching Placebo Gel in Blinded Phase	4
Open Label BHR-700 (0.2% 4-OHT Gel) Following BHR-700 in Blinded Phase	1
Open Label BHR-700 (0.2% 4-OHT Gel) Following Placebo in Blinded Phase	0

Change in Serum Concentration of Sex Hormone Binding Globulin (SHBG) From Baseline to Week 52/End of Study (EOS) Secondary · Blinded Phase: Baseline; Week 52/EOS

SHBG levels at baseline will be compared to levels at Week 52/EOS

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	0.1	± 1.6
Matching Placebo Gel	0.3	± 1.6

Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). Secondary · Blinded Phase: Baseline; Weeks 26, 52/EOS.

Lipid levels at baseline will be compared to levels measured at time-points in the study

Cholesterol (mmol/L) - Change from Baseline to Week 26

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	-0.1	± 0.6
Matching Placebo Gel	-0.2	± 0.7

Cholesterol (mmol/L) - Change from Baseline to Week 52/EOS

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	0.1	± 0.7
Matching Placebo Gel	0.0	± 0.7

Triglycerides (mmol/L) - Change from Baseline to Week 26

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	-0.2	± 1.2
Matching Placebo Gel	-0.2	± 0.6

Triglycerides (mmol/L) - Change from Baseline to Week 52/EOS

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	-0.1	± 0.8
Matching Placebo Gel	0.0	± 0.8

HDL Cholesterol (mmol/L) - Change from Baseline to Week 26

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	-0.0	± 0.3
Matching Placebo Gel	0.0	± 0.2

HDL Cholesterol (mmol/L) - Change from Baseline to Week 52/EOS

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	0.0	± 0.2
Matching Placebo Gel	0.0	± 0.3

LDL Cholesterol (mmol/L) - Change from Baseline to Week 26

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	0.0	± 0.6
Matching Placebo Gel	-0.1	± 0.7

LDL Cholesterol (mmol/L) - Change from Baseline to Week 52/EOS

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	0.1	± 0.5
Matching Placebo Gel	-0.0	± 0.7

Change in Serum Concentration of Select Bone Biomarkers: Bone Specific Alkaline Phosphatase (BSAP) (U/L) Secondary · Blinded Phase: Baseline; Week 52/EOS

Bone biomarker levels (BSAP) at baseline will be compared to levels measured at Week 52.

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	1.0	± 4.1
Matching Placebo Gel	0.7	± 3.3

Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit Secondary · Blinded Phase: Weeks 13, 26, 52/EOS

Blood samples will be taken to measure plasma concentrations of 4-OHT at time-points in the study

Week 13 E-4-OHT

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	12
BHR-700 (0.2% 4-OHT Gel)	128

Week 26 E-4-OHT

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	7
BHR-700 (0.2% 4-OHT Gel)	88

Week 52/EOS E-4-OHT

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	0
BHR-700 (0.2% 4-OHT Gel)	179

Week 13 Z-4-OHT

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	75
BHR-700 (0.2% 4-OHT Gel)	65

Week 26 Z-4-OHT

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	48
BHR-700 (0.2% 4-OHT Gel)	47

Week 52/EOS Z-4-OHT

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	16
BHR-700 (0.2% 4-OHT Gel)	163

Change in Serum Concentration of Select Bone Biomarkers:Type I Collagen C-Telopeptides (CTx) (pg/mL) Secondary · Blinded Phase: Baseline; Week 52/EOS

Bone biomarker levels (CTx) at baseline will be compared to levels measured at Week 52.

Group	Value	95% CI
BHR-700 (0.2% 4-OHT Gel)	-19.6	± 162
Matching Placebo Gel	3.7	± 155.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Blinded and Open Label Portions of the Study up to 104 Weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BHR-700 (0.2% 4-OHT Gel) in Blinded Phase

Serious: 5/149 (3%)

Deaths: 0/149

Matching Placebo Gel in Blinded Phase

Serious: 0/73 (0%)

Deaths: 0/73

Open Label BHR-700 (0.2% 4-OHT Gel) Following BHR-700 in Blinded Phase

Serious: 1/7 (14%)

Deaths: 0/7

Open Label BHR-700 (0.2% 4-OHT Gel) Following Placebo in Blinded Phase

Serious: 0/6 (0%)

Deaths: 0/6

Serious adverse events (4 terms)

Reaction	System	BHR-700 (0.2% 4-OHT Gel) i…	Matching Placebo Gel in Bl…	Open Label BHR-700 (0.2% 4…	Open Label BHR-700 (0.2% 4…
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Intraductal proliferative breast lesion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Endometrial adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Other adverse events (213 terms — click to expand)

Reaction	System	BHR-700 (0.2% 4-OHT Gel) i…	Matching Placebo Gel in Bl…	Open Label BHR-700 (0.2% 4…	Open Label BHR-700 (0.2% 4…
Nasopharyngitis	Infections and infestations	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Vulvovaginal mycotic infection	Infections and infestations	—	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—	—	—
Influenza	Infections and infestations	—	—	—	—
Breast pain	Reproductive system and breast disorders	—	—	—	—
Vaginal discharge	Reproductive system and breast disorders	—	—	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—	—	—
Hot flush	Vascular disorders	—	—	—	—
Respiratory tract infection	Infections and infestations	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Breast tenderness	Reproductive system and breast disorders	—	—	—	—
Vaginal haemorrhage	Reproductive system and breast disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Haemorrhoids	Gastrointestinal disorders	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—
Paraesthesia	Nervous system disorders	—	—	—	—
Body temperature increased	Investigations	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—
Diverticulitis	Infections and infestations	—	—	—	—
Pharyngitis	Infections and infestations	—	—	—	—
Bursitis	Musculoskeletal and connective tissue disorders	—	—	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Vulvovaginal discomfort	Reproductive system and breast disorders	—	—	—	—
Vulvovaginal pruritus	Reproductive system and breast disorders	—	—	—	—
Dysmenorrhoea	Reproductive system and breast disorders	—	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—	—
Toothache	Gastrointestinal disorders	—	—	—	—

Most-reported serious reactions: Invasive ductal breast carcinoma, Intraductal proliferative breast lesion, Endometrial adenocarcinoma, Pulmonary embolism.

Data from ClinicalTrials.gov NCT03199963 adverse events section.

Sponsor's own description

A study to determine the efficacy of 8 mg/day (4 mg/breast) of BHR-700 gel compared to placebo for reducing breast tissue density in women identified as having dense breast tissue upon analysis of screening mammography. The Primary Study Endpoint being the percent reduction of mammographic breast tissue density on a follow-up mammogram compared to the baseline mammogram after 52 weeks of treatment.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

Targeting nuclear hormone receptors for the prevention of breast cancer.
Moyer CL, Brown PH. · · 2023 · cited 11× · PMID 37583424 · DOI 10.3389/fmed.2023.1200947

Verify or expand the search:

Other BHR Pharma, LLC trials

Trials by the same sponsor.

NCT03202186 — Study of Progesterone in Treatment of Vasomotor Symptoms · Phase 3 · terminated

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT03199963 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by BHR Pharma, LLC
Last refreshed: 26 July 2022

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03199963.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing