A Multi-center 12-week Study of HMS5552 in T2DM

• Sponsor: Hua Medicine Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02561338
• Collaborator: Tigermed Consulting Co., Ltd (Industry)
• Enrollment: 258
• Location: 1
• Arms: 5
• Duration (Months): 12
• Patients Per Site Per Month: 21.5

Study Details

Study Description

Brief Summary

This study evaluates the safety, tolerability, efficacy and population PK of HMS5552 in type 2 diabetic adult subjects,there will be 5 groups ,4 groups will receive HMS5552,while 1 will receive placebo.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: HMS5552; Drug: HMS5552; Drug: HMS5552; Drug: HMS5552; Other: Placebo	Phase 2

Detailed Description

Glucokinase (GK, also called hexokinase IV or D) can phosphosphorylate glucose to glucose-6-phosphate (G-6-P) in pancreatic β-cells and liver cells, which represents the first step of glucose metabolism. GK also acts as a glucose sensor and exerts a key role in maintaining glucose homeostasis. HMS5552 is a 4th-generation GK agonist or activator (GKA), which was originally licensed from Roche and subsequently developed by Hua Medicine. HMS5552 has been shown to activate GK in pancreatic beta cells, liver and intestinal epithelial cells. It regulates systemic blood glucose through a variety of mechanisms including directly enhancing insulin release (pancreas), inhibiting production of endogenous glucose (liver) and by indirectly promoting GLP-1 release (enteroendocrine L-cells).

Study Design

• Study Type: Interventional
• Actual Enrollment: 258 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-blind, Placebo-controlled, 12-week Phase II Study to Evaluate the Safety, Tolerability, Efficacy and Population PK of HMS5552 in Type 2 Diabetic Adult Subjects
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HMS5552 dose 1 75mgQD oral administration	Drug: HMS5552; 75mgQD; Other Names: GKA
Experimental: HMS5552 dose 2 100mgQD oral administration	Drug: HMS5552; 100mgQD; Other Names: GKA
Experimental: HMS5552 dose 3 50mgBID oral administration	Drug: HMS5552; 50mgBID; Other Names: GKA
Experimental: HMS5552 dose 4 75mgBID oral administration	Drug: HMS5552; 75mgBID; Other Names: GKA
Placebo Comparator: Placebo Placebo, BID/QD oral administration	Other: Placebo; QD/BID

Outcome Measures

Primary Outcome Measures

1. After 12-week Treatment, the Change From Baseline in HbA1c [Baseline and 12 weeks]

   Assess the percentage of Hemoglobin A1c (HbA1c) changes at week 12. In the group HMS5552 dose3, a subject without follow-up data for HbA1c available was excluded. And in the group HMS5552 dose4, two subjects without follow-up data for HbA1c available were excluded. So the overall number of baseline participants is not consistent with numbers provided in any of the rows in the participant flow module.

Secondary Outcome Measures

1. Change From Baseline in 2hPPG [Baseline and 12 weeks]

   Using a standard meal tolerance test, to assess 2-h postprandial glucose (2hPPG). In this test, subjects were received meals standardised by China National Cereals, which supplied by Oils and Foodstuffs Corporation and contained 353 kcal, 75 g carbohydrate, 1.48 g fat, and 8.0 g protein. Collect the blood samples to detect blood glucose 2 hours after starting the meal.

2. Change From Baseline in FPG [Baseline and 12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male & female, 40~75 years old

2. T2DM patients，anti-hyperglycemic drug-naïve and on diet & exercise for at least 3 months, or with glucose controlled by Metformin or α-glucosidase inhibitor alone

3. HbA1c 7.5~10.5% at screening and pre-randomization

4. Fasting plasma glucose (FPG)7.0_{11.1 millimole/liter (mmol/L, local lab) at screening, and 7.0}13.3 millimole/liter (mmol/L, central lab) at pre-randomization

5. BMI: 19~30kg/m^2 & TG<5.5mmol/L

Exclusion Criteria:

1. T1D，secondary DM, pre-DM

2. kidney diseases or eGFR MDRD<60ml/min/1.73m^2

3. unstable CVDs

4. liver diseases

5. mental or CNS diseases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu	China

Sponsors and Collaborators

• Hua Medicine Limited
• Tigermed Consulting Co., Ltd

Investigators

• Principal Investigator: Dalong Zhu, MD，PhD, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hua Medicine Limited
• ClinicalTrials.gov Identifier: NCT02561338
• Other Study ID Numbers: HMM0201
• First Posted: Sep 28, 2015
• Last Update Posted: Mar 10, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Hua Medicine Limited: GKA,T2DM,HMS5552
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2

Study Results

Participant Flow

Arm/Group Title	HMS5552 Dose 1	HMS5552 Dose 2	HMS5552 Dose 3	HMS5552 Dose 4	Placebo
Arm/Group Description	HMS5552: 75mgQD	HMS5552: 100mgQD	HMS5552: 50mgBID	HMS5552: 75mgBID	Placebo, BID/QD
Period Title: Overall Study
STARTED	53	50	51	51	53
COMPLETED	45	44	42	46	51
NOT COMPLETED	8	6	9	5	2

Baseline Characteristics

Arm/Group Title	HMS5552 Dose 1	HMS5552 Dose 2	HMS5552 Dose 3	HMS5552 Dose 4	Placebo	Total
Arm/Group Description	HMS5552: 75mgQD	HMS5552: 100mgQD	HMS5552: 50mgBID	HMS5552: 75mgBID	Placebo: BID/QD	Total of all reporting groups
Overall Participants	53	50	50	49	53	255
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.58 (9.159)	56.7 (7.670)	54.92 (8.137)	55.42 (7.659)	54.73 (8.499)	55.88 (8.271)
Sex: Female, Male (Count of Participants)
Female	26 49.1%	22 44%	16 32%	18 36.7%	22 41.5%	104 40.8%
Male	27 50.9%	28 56%	34 68%	31 63.3%	31 58.5%	151 59.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	53 100%	50 100%	50 100%	49 100%	53 100%	255 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	53 100%	50 100%	50 100%	49 100%	53 100%	255 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
China	53 100%	50 100%	50 100%	49 100%	53 100%	255 100%
HbA1c (percentage of glycated hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycated hemoglobin]	8.44 (0.803)	8.27 (0.639)	8.33 (0.653)	8.46 (0.670)	8.39 (0.780)	8.38 (0.712)
FPG (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	9.933 (2.3356)	9.127 (1.4868)	9.390 (1.5317)	9.859 (1.9902)	9.277 (1.7608)	9.518 (1.8663)
2h PPG (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	18.042 (3.3004)	17.429 (3.2023)	17.243 (3.0943)	17.884 (3.1303)	16.950 (3.7282)	17.509 (3.3052)
Body Mass Index (BMI) units: kg/m^2 (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24.718 (2.8672)	25.010 (2.9374)	24.686 (2.3112)	25.321 (2.5419)	25.188 (2.6113)	25.321 (2.5419)
Diagnosis time (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.37 (4.053)	3.24 (4.304)	3.27 (4.220)	2.82 (3.230)	3.41 (4.195)	3.23 (3.984)

Outcome Measures

1. Primary Outcome

Title	After 12-week Treatment, the Change From Baseline in HbA1c
Description	Assess the percentage of Hemoglobin A1c (HbA1c) changes at week 12. In the group HMS5552 dose3, a subject without follow-up data for HbA1c available was excluded. And in the group HMS5552 dose4, two subjects without follow-up data for HbA1c available were excluded. So the overall number of baseline participants is not consistent with numbers provided in any of the rows in the participant flow module.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HMS5552 Dose 1	HMS5552 Dose 2	HMS5552 Dose 3	HMS5552 Dose 4	Placebo
Arm/Group Description	HMS5552: 75mgQD	HMS5552:100mgQD	HMS5552: 50mgBID	HMS5552: 75mgBID	Placebo:BID/QD
Measure Participants	53	50	50	49	53
Least Squares Mean (95% Confidence Interval) [Percentage of glycated hemoglobin]	-0.39	-0.65	-0.79	-1.12	-0.35

2. Secondary Outcome

Title	Change From Baseline in 2hPPG
Description	Using a standard meal tolerance test, to assess 2-h postprandial glucose (2hPPG). In this test, subjects were received meals standardised by China National Cereals, which supplied by Oils and Foodstuffs Corporation and contained 353 kcal, 75 g carbohydrate, 1.48 g fat, and 8.0 g protein. Collect the blood samples to detect blood glucose 2 hours after starting the meal.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HMS5552 Dose 1	HMS5552 Dose 2	HMS5552 Dose 3	HMS5552 Dose 4	Placebo
Arm/Group Description	HMS5552: 75mgQD	HMS5552:100mgQD	HMS5552: 50mgBID	HMS5552: 75mgBID	Placebo:BID/QD
Measure Participants	53	50	50	49	53
Mean (Standard Deviation) [mmol/L]	-4.669 (2.325)	-4.945 (3.387)	-3.898 (3.535)	-4.899 (3.921)	-1.987 (3.312)

3. Secondary Outcome

Title	Change From Baseline in FPG
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HMS5552 Dose 1	HMS5552 Dose 2	HMS5552 Dose 3	HMS5552 Dose 4	Placebo
Arm/Group Description	HMS5552: 75mgQD	HMS5552:100mgQD	HMS5552: 50mgBID	HMS5552: 75mgBID	Placebo:BID/QD
Measure Participants	53	50	50	49	53
Mean (Standard Deviation) [mmol/L]	-0.307 (2.000)	-0.382 (1.602)	-0.758 (2.150)	-1.319 (2.258)	-0.801 (1.752)

4. Post-Hoc Outcome

Title	Change From Baseline in MMTT (Mixed Meal Tolerance Test) β-cell Function Index
Description	Disposition index, i.e DI, by the insulin secretion sensitivity index-2 (ISSI-2). This is an calculated value which represents the ability of a person's pancreatic beta cells to lower blood glucose. A higher number means the pancreas is better able to secrete insulin and improve glucose levels. HOMA IR is an index used to evaluate the individual's insulin resistance level. The HOMA-IR index of normal individuals is 1. With the increase of insulin resistance, HOMA-IR index will be higher than 1.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Both of disposition index and HOMA-IR could reflect the function of β cell.

Arm/Group Title	HMS5552 Dose 1	HMS5552 Dose 2	HMS5552 Dose 3	HMS5552 Dose 4	Placebo
Arm/Group Description	HMS5552: 75mgQD	HMS5552: 100mgQD	HMS5552: 50mgBID	HMS5552: 75mgBID	Placebo, BID/QD
Measure Participants	53	50	50	49	53
Disposition Index	0.292	0.198	0.216	0.140	0.080
HOMA-IR	-0.530	-0.520	-0.550	-1.185	-0.680

Adverse Events

Time Frame	From randomization to 7 days after 12-week treatment
Adverse Event Reporting Description	Note: Hypoglycemia in this study was collected and analyzed as Special attention event separated from the analysis of Any other Advance Event. The Number Affected by Hypoglycemia was not included in the Total Number Affected by Any Other (Not including Serious) Adverse Event Above the Frequency Threshold in the third table.
Arm/Group Title	HMS5552 Dose 1		HMS5552 Dose 2		HMS5552 Dose 3		HMS5552 Dose 4		Placebo
Arm/Group Description	HMS5552: 75mgQD		HMS5552: 100mgQD		HMS5552: 50mgBID		HMS5552: 75mgBID		Placebo: BID/QD
All Cause Mortality
	HMS5552 Dose 1		HMS5552 Dose 2		HMS5552 Dose 3		HMS5552 Dose 4		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		0/50 (0%)		0/51 (0%)		0/51 (0%)		0/53 (0%)
Serious Adverse Events
	HMS5552 Dose 1		HMS5552 Dose 2		HMS5552 Dose 3		HMS5552 Dose 4		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/53 (1.9%)		1/50 (2%)		1/51 (2%)		0/51 (0%)		0/53 (0%)
Injury, poisoning and procedural complications
Right Achilles Tendon Rupture	0/53 (0%)	0	0/50 (0%)	0	1/51 (2%)	1	0/51 (0%)	0	0/53 (0%)	0
Nervous system disorders
Lacunar Infarction	1/53 (1.9%)	1	0/50 (0%)	0	0/51 (0%)	0	0/51 (0%)	0	0/53 (0%)	0
Right Cerebral Infarction Of Basal Ganglia	0/53 (0%)	0	1/50 (2%)	1	0/51 (0%)	0	0/51 (0%)	0	0/53 (0%)	0
Other (Not Including Serious) Adverse Events
	HMS5552 Dose 1		HMS5552 Dose 2		HMS5552 Dose 3		HMS5552 Dose 4		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/53 (30.2%)		21/50 (42%)		13/51 (25.5%)		18/51 (35.3%)		15/53 (28.3%)
Cardiac disorders
Ventricular Extrasystoles	0/53 (0%)	0	1/50 (2%)	1	0/51 (0%)	0	3/51 (5.9%)	3	0/53 (0%)	0
Hepatobiliary disorders
Hepatic Function Abnormal	2/53 (3.8%)	2	1/50 (2%)	1	3/51 (5.9%)	3	0/51 (0%)	0	1/53 (1.9%)	1
Infections and infestations
Upper Respiratory Tract Infection	6/53 (11.3%)	6	6/50 (12%)	6	1/51 (2%)	1	4/51 (7.8%)	5	3/53 (5.7%)	3
Urinary Tract Infection	1/53 (1.9%)	1	3/50 (6%)	3	0/51 (0%)	0	1/51 (2%)	1	3/53 (5.7%)	3
Nasopharyngitis	0/53 (0%)	0	1/50 (2%)	2	3/51 (5.9%)	3	0/51 (0%)	0	0/53 (0%)	0
Investigations
Protein Urine Present	3/53 (5.7%)	3	2/50 (4%)	2	0/51 (0%)	0	2/51 (3.9%)	2	1/53 (1.9%)	1
Blood Creatine Phosphokinase Increased	0/53 (0%)	0	1/50 (2%)	1	1/51 (2%)	1	1/51 (2%)	1	5/53 (9.4%)	5
White Blood Cells Urine Positive	1/53 (1.9%)	1	0/50 (0%)	0	2/51 (3.9%)	2	3/51 (5.9%)	3	1/53 (1.9%)	1
High Density Lipoprotein Decreased	1/53 (1.9%)	1	0/50 (0%)	0	1/51 (2%)	1	4/51 (7.8%)	4	1/53 (1.9%)	1
Metabolism and nutrition disorders
Hyperuricaemia	3/53 (5.7%)	3	6/50 (12%)	6	3/51 (5.9%)	3	4/51 (7.8%)	4	2/53 (3.8%)	2
Hypoglycemia	3/53 (5.7%)	8	2/50 (4%)	2	3/51 (5.9%)	3	3/51 (5.9%)	10	0/53 (0%)	0
Nervous system disorders
Dizziness	2/53 (3.8%)	4	4/50 (8%)	9	4/51 (7.8%)	6	0/51 (0%)	0	0/53 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.