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The combination of FF, an ICS and VI, an orally inhaled LABA has been developed as a once-daily combination therapy for the long-term maintenance treatment of asthma in adults and children >=12 years of age. Pivotal phase III studies have demonstrated the safety and efficacy of FF/VI in asthma. However, it is increasingly acknowledged that randomised clinical trials tend to be highly controlled and enrol a more highly selected subject population than is expected to be prescribed the medication post-approval. There is a need for data in a more representative population in close to a 'real life' conditions, where physicians have the ability to choose the best treatment in their view for any individual subject and adapt treatments to subjects' characteristics and response. This multi-center, open-label, randomized, parallel group study will evaluate the efficacy and safety of FF/VI compared with two usual ICS/LABA fixed combination (fluticasone propionate/salmeterol [FP/S] or budesonide/formoterol [BUD/F]) in subjects with persistent asthma, in a "close to real life" settings. FF/VI will be administered once-daily (QD) via ELLIPTA dry powder inhaler (DPI) and FP/S or BUD/F will be administered twice daily (BID) via DISKUS™ and TURBUHALER™ DPI respectively. ELLIPTA is a new powder inhaler designed to be easy to use. The total duration of subject participation will be approximately 6 months (24 weeks). ELLIPTA and DISKUS are registered trademarks of the GSK group of companies. TURBUHALER is a registered trademark of AstraZeneca.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fluticasone Furoate/Vilanterol | Experimental | Subjects will receive FF/VI 92 micrograms (mcg)/22 mcg or FF/VI 184 mcg/22 mcg as decided by the investigator QD via ELLIPTA DPI for 24 weeks. |
|
| FP/S OR BUD/F | Active Comparator | Subjects will receive FP/S (250 mcg/50 mcg or 500 mcg/50mcg) twice daily via DISKUS or BUD /F (200 mcg/6mcg or 400 mcg/12mcg one or two inhalations) twice daily via TURBUHALER DPI as decided by the investigator for 24 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fluticasone Furoate | Drug | FF 92 mcg or 184 mcg blended with lactose administered once daily via ELLIPTA DPI |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Asthma Control Test (ACT) Total Score at Week 12 | The ACT is a validated self-completed questionnaire consisting of 5 questions that evaluate asthma control during the past 4 weeks on a 5-point categorical scale. Total scores are calculated from the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that the participant's asthma is unlikely to be well controlled, whilst a score of 20 to 25 suggests that the participant's asthma is likely to be well controlled. Baseline value was the last assessment prior to randomization (Day 0). Change from Baseline was post-dose visit value minus the Baseline value. Least square mean change is presented. | Baseline and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in ACT Total Score at Week 24 | The ACT is a validated self-completed questionnaire consisting of 5 questions that evaluate asthma control on a 5-point categorical scale. Total scores are calculated from the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that the participant's asthma is unlikely to be well controlled, whilst a score of 20 to 25 suggests that the participant's asthma is likely to be well controlled. Baseline value was the last assessment prior to randomization (Day 0). Change from Baseline was post-dose visit value minus the Baseline value. Least square mean change is presented. |
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Inclusion Criteria:
Female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies:
Non-reproductive potential defined as: Pre-menopausal females with one of the following - Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause [refer to laboratory reference ranges for confirmatory levels]); Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until Week 24.
GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP:
This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis: Contraceptive subdermal implant that meets the Standard Operating Procedure (SOP) effectiveness criteria including a <1percent rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1 percent rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone; Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches; Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject; Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository); These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Amiens | 80090 | France | |||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30053956 | Derived | Devillier P, Humbert M, Boye A, Zachgo W, Jacques L, Nunn C, West S, Nicholls A, Antoun Z, Spinu L, Grouin JM. Efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI) versus twice-daily inhaled corticosteroids/long-acting beta2-agonists (ICS/LABA) in patients with uncontrolled asthma: An open-label, randomized, controlled trial. Respir Med. 2018 Aug;141:111-120. doi: 10.1016/j.rmed.2018.06.009. Epub 2018 Jun 9. |
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A total of 439 participants were screened for this study and 423 participants were randomized to treatment. Three of the randomized participants did not receive study treatment and were not included in the Intent-To-Treat (ITT) population.
A total of 439 participants with persistent asthma were screened. The study was conducted at 63 centers in 2 countries: 43 in France and 20 in Germany from 09 July 2015 to 20 July 2017. Age value being reported for all participants is an approximate age accurate to within + or -1 year.
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| ID | Title | Description |
|---|---|---|
| FG000 | Usual ICS/LABA | Eligible participants received fixed combination inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) (Fluticasone propionate [FP]/ Salmeterol [S] 250/50 micrograms [mcg] or 500/50 mcg, 1 inhalation twice daily; or Budesonide [BUD]/ Formoterol [F] 200/6 mcg or 400/12 mcg, 1 or 2 inhalations twice daily) for 24 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 28, 2016 | Mar 12, 2018 |
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| Vilanterol | Drug | Vilanterol 22 mcg blended with lactose and magnesium stearate administered once daily via ELLIPTA DPI |
|
| Fluticasone propionate | Drug | FP 250 mcg or 500 mcg blended with lactose administered twice daily via DISKUS DPI |
|
| Salmeterol | Drug | Salmeterol 50 mcg blended with lactose administered twice daily via DISKUS DPI |
|
| Budesonide | Drug | Budesonide 200 mcg or 400 mcg blended with lactose administered twice daily via TURBUHALER DPI |
|
| Formoterol Fumarate | Drug | Formoterol Furoate 6 mcg or 12 mcg blended with lactose administered twice daily via TURBUHALER DPI |
|
| Baseline and Week 24 |
| Percentage of Participants With Correct Use of Device, Defined as Not Making Any Critical or Non-critical Errors, at Week 12, and at Week 24 Independently of the Use at Week 12 | Participants were asked to read the appropriate package insert for their prescribed inhaler and then the investigator (or suitably qualified designee) demonstrated the proper use of the inhaler. The participant was then asked to self-administer their first dose of study treatment under the supervision of the investigator and any critical and non-critical errors were recorded. Individual instruments for assessing correct inhaler use were provided for each of the three devices used in this study. | Week 12 and Week 24 |
| Angers |
| 49000 |
| France |
| GSK Investigational Site | Avelin | 59710 | France |
| GSK Investigational Site | Bassussarry | 64200 | France |
| GSK Investigational Site | Beauzelle | 31700 | France |
| GSK Investigational Site | Bersée | 59235 | France |
| GSK Investigational Site | Bécon-les-Granits | 49370 | France |
| GSK Investigational Site | Béziers | 34500 | France |
| GSK Investigational Site | Biarritz | 64200 | France |
| GSK Investigational Site | Bourg-des-Comptes | 35890 | France |
| GSK Investigational Site | Broglie | 27270 | France |
| GSK Investigational Site | Bruay-la-Buissière | 62700 | France |
| GSK Investigational Site | Caen | 14000 | France |
| GSK Investigational Site | Cannes | 06614 | France |
| GSK Investigational Site | Carbon-Blanc | 33560 | France |
| GSK Investigational Site | Châtellerault | 86100 | France |
| GSK Investigational Site | Colombey-les-Belles | 54170 | France |
| GSK Investigational Site | Coulounieix-Chamiers | 24660 | France |
| GSK Investigational Site | Cournonterral | 34660 | France |
| GSK Investigational Site | Dessenheim | 68600 | France |
| GSK Investigational Site | Dijon | 21000 | France |
| GSK Investigational Site | Dinard | 35800 | France |
| GSK Investigational Site | Donges | 44480 | France |
| GSK Investigational Site | Ermont | 95124 | France |
| GSK Investigational Site | Fléville-devant-Nancy | 54710 | France |
| GSK Investigational Site | Gémenos | 13420 | France |
| GSK Investigational Site | Gondreville | 54840 | France |
| GSK Investigational Site | Grenay | 62160 | France |
| GSK Investigational Site | Guesnain | 59287 | France |
| GSK Investigational Site | Hatten | 67690 | France |
| GSK Investigational Site | Hinx | 40180 | France |
| GSK Investigational Site | La Bouëxière | 35340 | France |
| GSK Investigational Site | La Fôret Sur Sèvres | 79380 | France |
| GSK Investigational Site | La Riche | 37520 | France |
| GSK Investigational Site | Lambersart | 59130 | France |
| GSK Investigational Site | Laval | 53000 | France |
| GSK Investigational Site | Le Blanc-Mesnil | 93150 | France |
| GSK Investigational Site | Limoges | 87000 | France |
| GSK Investigational Site | Marseille | 13331 | France |
| GSK Investigational Site | Metz-Tessy | 74370 | France |
| GSK Investigational Site | Montauban | 82017 | France |
| GSK Investigational Site | Montpellier | 34070 | France |
| GSK Investigational Site | Montpellier | 34295 | France |
| GSK Investigational Site | Mûrs-Erigné | 49610 | France |
| GSK Investigational Site | Nancy | 54000 | France |
| GSK Investigational Site | Nantes | 44200 | France |
| GSK Investigational Site | Nantes | 44300 | France |
| GSK Investigational Site | Narbonne | 11100 | France |
| GSK Investigational Site | Nice | 06000 | France |
| GSK Investigational Site | Obernai | 67210 | France |
| GSK Investigational Site | Paris | 75020 | France |
| GSK Investigational Site | Perpignan | 66000 | France |
| GSK Investigational Site | Rosiers-d'Égletons | 19300 | France |
| GSK Investigational Site | Rouen | 76000 | France |
| GSK Investigational Site | Royaumeix | 54200 | France |
| GSK Investigational Site | Saint-Etienne | 42000 | France |
| GSK Investigational Site | Saint-Etienne | 42100 | France |
| GSK Investigational Site | Saint-Ouen-la-Rouërie | 35460 | France |
| GSK Investigational Site | Scorbé-Clairvaux | 86140 | France |
| GSK Investigational Site | Segré | 49500 | France |
| GSK Investigational Site | Soulac-sur-Mer | 33780 | France |
| GSK Investigational Site | Strasbourg | 67000 | France |
| GSK Investigational Site | Thouars | 79100 | France |
| GSK Investigational Site | Toul | 54200 | France |
| GSK Investigational Site | Toulon | 83000 | France |
| GSK Investigational Site | Toulouse | 31077 | France |
| GSK Investigational Site | Toulouse | 31300 | France |
| GSK Investigational Site | Verzy | 51380 | France |
| GSK Investigational Site | Vieux-Condé | 59690 | France |
| GSK Investigational Site | Villejuif | 94800 | France |
| GSK Investigational Site | Wattrelos | 59150 | France |
| GSK Investigational Site | Witry-lès-Reims | 51420 | France |
| GSK Investigational Site | Munich | Bavaria | 80339 | Germany |
| GSK Investigational Site | Munich | Bavaria | 81241 | Germany |
| GSK Investigational Site | Wallerfing | Bavaria | 94574 | Germany |
| GSK Investigational Site | Potsdam | Brandenburg | 14469 | Germany |
| GSK Investigational Site | Dortmund | North Rhine-Westphalia | 44263 | Germany |
| GSK Investigational Site | Rheine | North Rhine-Westphalia | 48431 | Germany |
| GSK Investigational Site | Delitzsch | Saxony | 04509 | Germany |
| GSK Investigational Site | Leipzg | Saxony | 04109 | Germany |
| GSK Investigational Site | Leipzig | Saxony | 04103 | Germany |
| GSK Investigational Site | Leipzig | Saxony | 04207 | Germany |
| GSK Investigational Site | Leipzig | Saxony | 04275 | Germany |
| GSK Investigational Site | Leipzig | Saxony | 04357 | Germany |
| GSK Investigational Site | Teuchern | Saxony-Anhalt | 6682 | Germany |
| GSK Investigational Site | Geesthacht | Schleswig-Holstein | 21502 | Germany |
| GSK Investigational Site | Schmölln | Thuringia | 04626 | Germany |
| GSK Investigational Site | Berlin | 10119 | Germany |
| GSK Investigational Site | Berlin | 10717 | Germany |
| GSK Investigational Site | Berlin | 10787 | Germany |
| GSK Investigational Site | Berlin | 13156 | Germany |
| GSK Investigational Site | Berlin | 14059 | Germany |
| GSK Investigational Site | Magdeburg | 39120 | Germany |
| FG001 |
| FF/VI |
Eligible participants received Fluticasone Furoate (FF)/ Vilanterol (VI) 100 mcg/22 mcg or FF/VI 200 mcg/25 mcg 1 inhalation once daily for 24 weeks. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
ITT Population comprised of all randomized participants who received at least one dose of the prescription of study medication (either FF/VI or usual ICS/LABA).
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| ID | Title | Description |
|---|---|---|
| BG000 | Usual ICS/LABA | Eligible participants received fixed combination ICS/LABA (FP/S 250/50 mcg or 500/50 mcg, 1 inhalation twice daily; or BUD/F 200/6 mcg or 400/12 mcg, 1 or 2 inhalations twice daily) for 24 weeks. |
| BG001 | FF/VI | Eligible participants received Fluticasone FF/Vilanterol VI 100 mcg/22 mcg or FF/VI 200 mcg/25 mcg 1 inhalation once daily for 24 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Asthma Control Test (ACT) Total Score at Week 12 | The ACT is a validated self-completed questionnaire consisting of 5 questions that evaluate asthma control during the past 4 weeks on a 5-point categorical scale. Total scores are calculated from the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that the participant's asthma is unlikely to be well controlled, whilst a score of 20 to 25 suggests that the participant's asthma is likely to be well controlled. Baseline value was the last assessment prior to randomization (Day 0). Change from Baseline was post-dose visit value minus the Baseline value. Least square mean change is presented. | ITT Population. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Scores on a Scale | Baseline and Week 12 |
|
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| Secondary | Change From Baseline in ACT Total Score at Week 24 | The ACT is a validated self-completed questionnaire consisting of 5 questions that evaluate asthma control on a 5-point categorical scale. Total scores are calculated from the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that the participant's asthma is unlikely to be well controlled, whilst a score of 20 to 25 suggests that the participant's asthma is likely to be well controlled. Baseline value was the last assessment prior to randomization (Day 0). Change from Baseline was post-dose visit value minus the Baseline value. Least square mean change is presented. | ITT Population. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Scores on a Scale | Baseline and Week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Correct Use of Device, Defined as Not Making Any Critical or Non-critical Errors, at Week 12, and at Week 24 Independently of the Use at Week 12 | Participants were asked to read the appropriate package insert for their prescribed inhaler and then the investigator (or suitably qualified designee) demonstrated the proper use of the inhaler. The participant was then asked to self-administer their first dose of study treatment under the supervision of the investigator and any critical and non-critical errors were recorded. Individual instruments for assessing correct inhaler use were provided for each of the three devices used in this study. | ITT Population. Only those participants available at the specified time points were analyzed. | Posted | Number | Percentage of participants | Week 12 and Week 24 |
|
On-treatment serious adverse events (SAEs) and non-serious adverse drug reactions were collected from start of study treatment up to Week 24
On-treatment SAEs and non-serious adverse drug reactions were collected for the Safety Population comprised of all enrolled participants who received at least one dose of study medication (either FF/VI or usual ICS/LABA) and considered as-treated.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Usual ICS/LABA | Eligible participants received fixed combination ICS/LABA (FP/S 250/50 mcg or 500/50 mcg, 1 inhalation twice daily; or BUD/F 200/6 mcg or 400/12 mcg, 1 or 2 inhalations twice daily) for 24 weeks. | 0 | 210 | 4 | 210 | 0 | 210 |
| EG001 | FF/VI | Eligible participants received Fluticasone FF/Vilanterol VI 100 mcg/22 mcg or FF/VI 200 mcg/25 mcg 1 inhalation once daily for 24 weeks. | 0 | 209 | 3 | 209 | 0 | 209 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chronic sinusitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Labyrinthitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Ovarian abscess | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Adnexa uteri pain | Reproductive system and breast disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Varicose vein ruptured | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 21, 2017 | Mar 12, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C523187 | fluticasone furoate |
| C550468 | vilanterol |
| D000068298 | Fluticasone |
| D000068299 | Salmeterol Xinafoate |
| D019819 | Budesonide |
| D000068759 | Formoterol Fumarate |
| ID | Term |
|---|---|
| D000730 | Androstadienes |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D000420 | Albuterol |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
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| Male |
|
| Asian - Central/South Asian Heritage |
|
| Asian - East Asian Heritage |
|
| Asian - South East Asian Heritage |
|
| Native Hawaiian Or Other Pacific Islander |
|
| White - Arabic/North African Heritage |
|
| White - White/Caucasian/European Heritage |
|
| Mixed White Race |
|
| Units | Counts |
|---|---|
| Participants |
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| Units |
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| Counts |
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| Participants |
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