A Dose Range Finding Study to Evaluate the Effect of Bexa... | NCT02390050

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Bexagliflozin tablets, 5 mg	Active Comparator	Bexagliflozin tablets, 5 mg, once daily by mouth before breakfast	Drug: Bexagliflozin tablets
Bexagliflozin tablets, 10 mg	Active Comparator	Bexagliflozin tablets, 10 mg, once daily by mouth before breakfast	Drug: Bexagliflozin tablets
Bexagliflozin tablets, 20 mg	Active Comparator	Bexagliflozin tablets, 20 mg, once daily by mouth before breakfast	Drug: Bexagliflozin tablets
Bexagliflozin tablets, placebo	Placebo Comparator	Bexagliflozin tablets, placebo, once daily by mouth before breakfast	Drug: Bexagliflozin tablets, placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bexagliflozin tablets	Drug	Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablets, 10 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in HbA1c After 12 Weeks of Treatment	Mixed model repeated measures (MMRM) analysis of covariance model (ANCOVA) with baseline HbA1c as a covariate will be fit to the available data, incorporating all visits at which HbA1c was measured for each subject including scheduled visits at Weeks 2, 6, and 12 as well as unscheduled visits for measurements of HbA1c. Treatment (placebo, 5 mg, 10 mg, 20 mg), study center, prior anti-diabetic treatment status, study visit and treatment-by-visit interaction will be applied as fixed effects and subject as a random effect. The least square mean (LSM) change from baseline to Week 12 was analyzed using the Mixed-Effect Model Repeated Measure (MMRM) Analysis of Covariance (ANCOVA) model using 95% Confidence Intervals (CIs) for the between-group mean changes.	12 weeks

Secondary Outcomes

Measure	Description	Time Frame
Proportion of Subjects With HbA1c < 7%	To assess the efficacy of bexagliflozin based on the proportion of subjects who reach the American Diabetes Associate (ADA) and the Japan Diabetes Society target HbA1c of <7%.	Baseline to up to 12 weeks
Change in Body Weight Over Time

Eligibility Module

Eligibility Criteria

The following subjects were eligible for randomization:

men or women ≥ 20 years of age at screening. Women of childbearing potential must test negative by urine pregnancy test.
were treatment naïve or taking one oral anti-diabetic medication in combination with diet and exercise
were diagnosed with T2DM with HbA1c levels at screening between 7.0% and 8.5% (inclusive) if treatment naïve or with HbA1c levels between 6.5 and 8.5% (inclusive) if on one oral anti-diabetic medication
had a body mass index (BMI) ≤ 40 kg/m2
were taking stable doses of medication for hypertension or hyperlipidemia that has not changed for at least 30 days prior to screening (if applicable)
were able to comprehend the study participation requirements and willing to provide written informed consent in accordance with institutional and regulatory guidelines
were able to maintain adequate glycemic control at the run-in visit (for subjects who complete the washout)
had an HbA1c between 7.0 and 8.5% (inclusive) prior to randomization (day -3 to -5)
were capable of adhering to the investigational product administration requirements as evidenced by omission of no more than one dose of run-in medication

Subjects who exhibited any of the following characteristics were to be ineligible for randomization:

Diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young
Used parenteral therapy for treatment of diabetes
Pregnancy or current breastfeeding status
Hemoglobinopathy or carrier status for hemoglobin alleles that affect HbA1c measurement
Genitourinary tract infection within 6 weeks of screening or history of ≥3 genitourinary infections requiring treatment within 6 months of screening
Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at screening.
Uncontrolled hypertension at screening
A positive result on hepatitis B surface antigen, hepatitis C, or positive result from screen for drugs of abuse
History of human immunodeficiency virus infection
Life expectancy < 2 years
History of New York Heart Association Class 4 heart failure within 3 months of screening
History of myocardial infarction, unstable angina, stroke, or hospitalization for heart failure within 3 months of screening
History of treatment with an investigational drug within 30 days or within 7 half lives of the investigational drug, whichever is longer
Previous treatment with bexagliflozin
Had taken or within 6 months of taking any Sodium Glucose Transporter 2 (SGLT2) inhibitors prior to screening
Participation of another interventional trial
Not able to comply with the study scheduled visits
Affected by any condition, disease, disorder, or clinically relevant abnormality that, in the opinion of the investigator, would jeopardize the subject's appropriate participation in this study.
Liver function tests resulting in Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 2.5 x upper limit of normal (ULN) or total bilirubin ≥ 1.5 x ULN, with the exception of isolated Gilbert's syndrome ,at screening
Exhibited fasting plasma glucose ≥ 250 mg/dL (13.9 mmol/L) on two or more consecutive days prior to randomization or exhibited severe clinical signs or symptoms of hyperglycemia during the washout or run-in periods, including weight loss, blurred vision, increased thirst, or increased urination, or fatigue
Fasting Plasma Glucose ≥ 250 mg/dL at randomization
Prior renal transplantation or evidence of nephrotic syndrome, defined as a urine albumin-to-creatinine ratio (UACR) > 2000 mg/g at screening

Name	Affiliation	Role
J Paul Lock, M.D.	Theracos	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Phoenix Medical Research Institute LLC		Peoria	Arizona	85381	United States
Advanced Arizona Clinical Research

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
24357209	Background	American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80. doi: 10.2337/dc14-S014. No abstract available.
23796131	Background	Look AHEAD Research Group; Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow RS, Curtis JM, Egan CM, Espeland MA, Evans M, Foreyt JP, Ghazarian S, Gregg EW, Harrison B, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Kitabchi AE, Knowler WC, Lewis CE, Maschak-Carey BJ, Montez MG, Murillo A, Nathan DM, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Reboussin D, Regensteiner JG, Rickman AD, Ryan DH, Safford M, Wadden TA, Wagenknecht LE, West DS, Williamson DF, Yanovski SZ. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013 Jul 11;369(2):145-54. doi: 10.1056/NEJMoa1212914. Epub 2013 Jun 24.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
FG001	Bexagliflozin 5 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 16, 2015	Apr 1, 2020

Arm/Group Information

ID	Title	Description
BG000	Placebo	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
BG001	Bexagliflozin 5 mg	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
BG002	Bexagliflozin 10 mg	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
BG003	Bexagliflozin 20 mg	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00058.8± 10.42 BG00159.0± 10.22 BG00259.4± 8.99 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00030 BG00125 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00014 BG00117 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00036 BG00136 BG002

Height

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG000165.6± 10.63 BG001165.7± 9.25 BG002

Body Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00078.72± 19.747 BG00180.52± 18.977 BG002

BMI

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00028.54± 5.535 BG00129.10± 5.211 BG002

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 in HbA1c After 12 Weeks of Treatment

Mixed model repeated measures (MMRM) analysis of covariance model (ANCOVA) with baseline HbA1c as a covariate will be fit to the available data, incorporating all visits at which HbA1c was measured for each subject including scheduled visits at Weeks 2, 6, and 12 as well as unscheduled visits for measurements of HbA1c. Treatment (placebo, 5 mg, 10 mg, 20 mg), study center, prior anti-diabetic treatment status, study visit and treatment-by-visit interaction will be applied as fixed effects and subject as a random effect. The least square mean (LSM) change from baseline to Week 12 was analyzed using the Mixed-Effect Model Repeated Measure (MMRM) Analysis of Covariance (ANCOVA) model using 95% Confidence Intervals (CIs) for the between-group mean changes.

Subjects who were randomized, took at least one dose of double-blind study medication, and had at least one post-randomization HbA1c measurement were included in the full analysis dataset (FAS). TheHbA1c change from baseline through 12 weeks, and the primary analysis is based on the available data and data obtained after rescue will be excluded and considered missing.

Posted

Least Squares Mean

Standard Error

percentage of glycated hemoglobin

12 weeks

ID	Title	Description
OG000	Placebo	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG001	Bexagliflozin 5 mg	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG002	Bexagliflozin 10 mg	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG003	Bexagliflozin 20 mg	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.

Units	Counts
Participants	OG00064 OG00165 OG00268 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.24± 0.08 OG001-0.31± 0.08 OG002-0.44± 0.08 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates	< 0.0001	P-value from Type III F-test	Difference of LS Means	-0.55			2-Sided	95	-0.76	-0.34					Superiority
OG000 OG002

Secondary

Proportion of Subjects With HbA1c < 7%

To assess the efficacy of bexagliflozin based on the proportion of subjects who reach the American Diabetes Associate (ADA) and the Japan Diabetes Society target HbA1c of <7%.

Subjects with at least one post-baseline HbA1c value <7% met this endpoint. HbA1c values obtained after start of rescue medication were excluded from this analysis. The number and percentage of subjects with at least one HbA1c value <7% were summarized by treatment group for the FAS.

Posted

Count of Participants

Participants

Baseline to up to 12 weeks

ID	Title	Description
OG000	Placebo	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG001	Bexagliflozin 5 mg	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG002	Bexagliflozin 10 mg	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.

Secondary

Change in Body Weight Over Time

The body weight was analyzed on the full analysis set using the MMRM ANCOVA model used for the primary efficacy analysis.

Only subject with a value at the specified time is included

Posted

Least Squares Mean

Standard Error

Baseline to Week 2, Week 6 and Week 12

ID	Title	Description
OG000	Placebo	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG001	Bexagliflozin 5 mg	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG002	Bexagliflozin 10 mg	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG003	Bexagliflozin 20 mg

Secondary

Change in Fasting Plasma Glucose (FPG) Over Time

The fasting plasma glucose (FPG) was analyzed on the full analysis set using the same MMRM ANCOVA model used in the primary efficacy analysis.

Only subject with a value at the specified time is included

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline to Week 2, Week 6 and Week 12

ID	Title	Description
OG000	Placebo	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG001	Bexagliflozin 5 mg	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG002	Bexagliflozin 10 mg	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG003	Bexagliflozin 20 mg

Secondary

Change in Systolic and Diastolic Blood Pressure Over Time

The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were analyzed on the full analysis set using the same MMRM ANCOVA model used in the primary efficacy analysis.

Only subject with a value at the specified time is included

Posted

Least Squares Mean

Standard Error

mm Hg

Baseline to Week 2, Week 6 and Week 12

ID	Title	Description
OG000	Placebo	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG001	Bexagliflozin 5 mg	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG002	Bexagliflozin 10 mg	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG003	Bexagliflozin 20 mg

Secondary

Change in HbA1c Over Time

The least square mean (LSM) change from baseline to Week 2, Week 6 and Week 12 was analyzed using the Mixed-Effect Model Repeated Measure (MMRM) Analysis of Covariance (ANCOVA) model using 95% Confidence Intervals (CIs) for the between-group mean changes. The LSM change was calculated by excluding HbA1c data obtained after rescue medication.

Only subject with a value at the specified time is included

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline to Week 2, Week 6 and Week 12

ID	Title	Description
OG000	Placebo	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG001	Bexagliflozin 5 mg	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
OG002	Bexagliflozin 10 mg	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	72	0	72	12	72
EG001	Bexagliflozin 5 mg	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	72	0	72	15	72
EG002	Bexagliflozin 10 mg	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	72	3	72	18	72
EG003	Bexagliflozin 20 mg	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	76	2	76	17	76

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0010 affected72 at risk EG0021 affected72 at risk EG0030 affected76 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0010 affected72 at risk EG0021 affected72 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0010 affected72 at risk EG0021 affected72 at risk EG003
Urinary Tract Infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0010 affected72 at risk EG0020 affected72 at risk EG003
Gastroesophageal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0010 affected72 at risk EG0020 affected72 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0003 affected72 at risk EG0015 affected72 at risk EG0024 affected72 at risk EG0033 affected76 at risk
Pharyngitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0012 affected72 at risk EG0023 affected72 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected72 at risk EG0012 affected72 at risk EG0021 affected72 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0010 affected72 at risk EG0022 affected72 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0002 affected72 at risk EG0010 affected72 at risk EG0021 affected72 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected72 at risk EG0010 affected72 at risk EG0020 affected72 at risk EG003
Polyuria	Renal and urinary disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0010 affected72 at risk EG0020 affected72 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0012 affected72 at risk EG0022 affected72 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected72 at risk EG0010 affected72 at risk EG0022 affected72 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected72 at risk EG0011 affected72 at risk EG0020 affected72 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0011 affected72 at risk EG0022 affected72 at risk EG003
Dizziness	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected72 at risk EG0012 affected72 at risk EG0020 affected72 at risk EG003
Headache	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected72 at risk EG0012 affected72 at risk EG0022 affected72 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected72 at risk EG0010 affected72 at risk EG0020 affected72 at risk EG003
Diarrhea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected72 at risk EG0012 affected72 at risk EG0021 affected72 at risk EG003
Hypoglycemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected72 at risk EG0010 affected72 at risk EG0020 affected72 at risk EG003
Vision blurred	Eye disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0012 affected72 at risk EG0020 affected72 at risk EG003
Thirst	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0010 affected72 at risk EG0020 affected72 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0010 affected72 at risk EG0020 affected72 at risk EG003
Balanoposthitis	Reproductive system and breast disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected72 at risk EG0010 affected72 at risk EG0020 affected72 at risk EG003

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases