Trial Outcomes & Findings for Dose-Ranging Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Metformin Delayed Release in Subjects With T2DM (NCT NCT02526524)

NCT ID: NCT02526524

Last Updated: 2018-04-27

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

571 participants

Primary outcome timeframe

Baseline and 16 weeks after the first dose of study medication

Results posted on

2018-04-27

Participant Flow

Participant milestones

Participant milestones
Measure
600 mg Met DR qAM
600 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
900 mg Met DR qAM
900 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1200 mg Met DR qAM
1200 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1500 mg Met DR qAM
1500 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
Placebo
placebo match for 600 and 1200 mg Met DR qAM treatment groups (Placebo 1) and placebo match for 900 and 1500 mg Met DR qAM treatment groups (Placebo 2) Placebo
2000 mg Met IR
1000 mg metformin immediate-release twice daily Met IR: metformin immediate-release tablets
Overall Study
STARTED
94
95
96
96
96
94
Overall Study
COMPLETED
82
86
70
89
72
73
Overall Study
NOT COMPLETED
12
9
26
7
24
21

Reasons for withdrawal

Reasons for withdrawal
Measure
600 mg Met DR qAM
600 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
900 mg Met DR qAM
900 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1200 mg Met DR qAM
1200 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1500 mg Met DR qAM
1500 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
Placebo
placebo match for 600 and 1200 mg Met DR qAM treatment groups (Placebo 1) and placebo match for 900 and 1500 mg Met DR qAM treatment groups (Placebo 2) Placebo
2000 mg Met IR
1000 mg metformin immediate-release twice daily Met IR: metformin immediate-release tablets
Overall Study
Withdrawal by Subject
3
3
6
1
9
5
Overall Study
Adverse Event
3
2
4
2
6
8
Overall Study
Lost to Follow-up
2
3
8
1
2
5
Overall Study
Protocol Violation
3
1
5
3
4
3
Overall Study
Loss of Glucose Control
0
0
3
0
2
0
Overall Study
Physician Decision
0
0
0
0
1
0
Overall Study
Sponsor Decision
1
0
0
0
0
0

Baseline Characteristics

Dose-Ranging Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Metformin Delayed Release in Subjects With T2DM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
600 mg Met DR qAM
n=94 Participants
600 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
900 mg Met DR qAM
n=95 Participants
900 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1200 mg Met DR qAM
n=96 Participants
1200 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1500 mg Met DR qAM
n=96 Participants
1500 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
Placebo
n=96 Participants
placebo match for 600 and 1200 mg Met DR qAM treatment groups (Placebo 1) and placebo match for 900 and 1500 mg Met DR qAM treatment groups (Placebo 2) Placebo
2000 mg Met IR
n=94 Participants
1000 mg metformin immediate-release twice daily Met IR: metformin immediate-release tablets
Total
n=571 Participants
Total of all reporting groups
Age, Continuous
56 years
STANDARD_DEVIATION 10.2 • n=5 Participants
55 years
STANDARD_DEVIATION 10.5 • n=7 Participants
55 years
STANDARD_DEVIATION 11.1 • n=5 Participants
55 years
STANDARD_DEVIATION 8.9 • n=4 Participants
57 years
STANDARD_DEVIATION 11.0 • n=21 Participants
57 years
STANDARD_DEVIATION 11.1 • n=8 Participants
56 years
STANDARD_DEVIATION 10.5 • n=8 Participants
Sex: Female, Male
Female
46 Participants
n=5 Participants
38 Participants
n=7 Participants
45 Participants
n=5 Participants
42 Participants
n=4 Participants
53 Participants
n=21 Participants
45 Participants
n=8 Participants
269 Participants
n=8 Participants
Sex: Female, Male
Male
48 Participants
n=5 Participants
57 Participants
n=7 Participants
51 Participants
n=5 Participants
54 Participants
n=4 Participants
43 Participants
n=21 Participants
49 Participants
n=8 Participants
302 Participants
n=8 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
36 Participants
n=5 Participants
44 Participants
n=7 Participants
41 Participants
n=5 Participants
42 Participants
n=4 Participants
37 Participants
n=21 Participants
45 Participants
n=8 Participants
245 Participants
n=8 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
58 Participants
n=5 Participants
51 Participants
n=7 Participants
55 Participants
n=5 Participants
54 Participants
n=4 Participants
59 Participants
n=21 Participants
49 Participants
n=8 Participants
326 Participants
n=8 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=8 Participants
0 Participants
n=8 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
1 Participants
n=8 Participants
2 Participants
n=8 Participants
Race (NIH/OMB)
Asian
3 Participants
n=5 Participants
6 Participants
n=7 Participants
3 Participants
n=5 Participants
3 Participants
n=4 Participants
5 Participants
n=21 Participants
2 Participants
n=8 Participants
22 Participants
n=8 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
1 Participants
n=21 Participants
0 Participants
n=8 Participants
2 Participants
n=8 Participants
Race (NIH/OMB)
Black or African American
14 Participants
n=5 Participants
7 Participants
n=7 Participants
23 Participants
n=5 Participants
19 Participants
n=4 Participants
17 Participants
n=21 Participants
8 Participants
n=8 Participants
88 Participants
n=8 Participants
Race (NIH/OMB)
White
75 Participants
n=5 Participants
82 Participants
n=7 Participants
70 Participants
n=5 Participants
73 Participants
n=4 Participants
72 Participants
n=21 Participants
82 Participants
n=8 Participants
454 Participants
n=8 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
1 Participants
n=8 Participants
2 Participants
n=8 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
1 Participants
n=21 Participants
0 Participants
n=8 Participants
1 Participants
n=8 Participants
Body Weight
94 kg
STANDARD_DEVIATION 19.9 • n=5 Participants
89 kg
STANDARD_DEVIATION 18.5 • n=7 Participants
93 kg
STANDARD_DEVIATION 20.9 • n=5 Participants
95 kg
STANDARD_DEVIATION 22.2 • n=4 Participants
86 kg
STANDARD_DEVIATION 17.1 • n=21 Participants
89 kg
STANDARD_DEVIATION 21.3 • n=8 Participants
91 kg
STANDARD_DEVIATION 20.2 • n=8 Participants
Body Mass Index
33 kg/m²
STANDARD_DEVIATION 5.1 • n=5 Participants
32 kg/m²
STANDARD_DEVIATION 5.5 • n=7 Participants
32 kg/m²
STANDARD_DEVIATION 5.9 • n=5 Participants
33 kg/m²
STANDARD_DEVIATION 5.8 • n=4 Participants
31 kg/m²
STANDARD_DEVIATION 5.1 • n=21 Participants
32 kg/m²
STANDARD_DEVIATION 5.4 • n=8 Participants
32 kg/m²
STANDARD_DEVIATION 5.5 • n=8 Participants
HbA1c
8.6 %
STANDARD_DEVIATION 0.85 • n=5 Participants
8.7 %
STANDARD_DEVIATION 0.82 • n=7 Participants
8.7 %
STANDARD_DEVIATION 0.90 • n=5 Participants
8.6 %
STANDARD_DEVIATION 0.94 • n=4 Participants
8.6 %
STANDARD_DEVIATION 0.87 • n=21 Participants
8.6 %
STANDARD_DEVIATION 0.92 • n=8 Participants
8.6 %
STANDARD_DEVIATION 0.88 • n=8 Participants
HbA1c stratum
<8.5%
45 Participants
n=5 Participants
45 Participants
n=7 Participants
46 Participants
n=5 Participants
46 Participants
n=4 Participants
45 Participants
n=21 Participants
45 Participants
n=8 Participants
272 Participants
n=8 Participants
HbA1c stratum
≥8.5%
49 Participants
n=5 Participants
50 Participants
n=7 Participants
50 Participants
n=5 Participants
50 Participants
n=4 Participants
51 Participants
n=21 Participants
49 Participants
n=8 Participants
299 Participants
n=8 Participants
Fasting Plasma Glucose
204 mg/dL
STANDARD_DEVIATION 58.1 • n=5 Participants
202 mg/dL
STANDARD_DEVIATION 45.3 • n=7 Participants
205 mg/dL
STANDARD_DEVIATION 59.0 • n=5 Participants
212 mg/dL
STANDARD_DEVIATION 53.5 • n=4 Participants
204 mg/dL
STANDARD_DEVIATION 57.3 • n=21 Participants
200 mg/dL
STANDARD_DEVIATION 50.3 • n=8 Participants
205 mg/dL
STANDARD_DEVIATION 54.0 • n=8 Participants
Diabetes Duration
6.6 years
STANDARD_DEVIATION 5.20 • n=5 Participants
8.8 years
STANDARD_DEVIATION 8.01 • n=7 Participants
7.3 years
STANDARD_DEVIATION 6.25 • n=5 Participants
7.6 years
STANDARD_DEVIATION 5.99 • n=4 Participants
8.3 years
STANDARD_DEVIATION 6.99 • n=21 Participants
8.6 years
STANDARD_DEVIATION 7.13 • n=8 Participants
7.9 years
STANDARD_DEVIATION 6.67 • n=8 Participants
Estimated Glomerular Filtration Rate
94.4 mL/min/1.73m²
STANDARD_DEVIATION 19.05 • n=5 Participants
94.5 mL/min/1.73m²
STANDARD_DEVIATION 22.83 • n=7 Participants
96.2 mL/min/1.73m²
STANDARD_DEVIATION 24.48 • n=5 Participants
95.9 mL/min/1.73m²
STANDARD_DEVIATION 22.77 • n=4 Participants
96.4 mL/min/1.73m²
STANDARD_DEVIATION 27.42 • n=21 Participants
96.2 mL/min/1.73m²
STANDARD_DEVIATION 22.42 • n=8 Participants
95.6 mL/min/1.73m²
STANDARD_DEVIATION 23.22 • n=8 Participants
Estimated Glomerular Filtration Rate Subgroup
<90 mL/min/1.73m²
42 Participants
n=5 Participants
46 Participants
n=7 Participants
36 Participants
n=5 Participants
42 Participants
n=4 Participants
42 Participants
n=21 Participants
43 Participants
n=8 Participants
251 Participants
n=8 Participants
Estimated Glomerular Filtration Rate Subgroup
≥90 mL/min/1.73m²
52 Participants
n=5 Participants
49 Participants
n=7 Participants
60 Participants
n=5 Participants
54 Participants
n=4 Participants
54 Participants
n=21 Participants
51 Participants
n=8 Participants
320 Participants
n=8 Participants
Prior Metformin Use
40 Participants
n=5 Participants
47 Participants
n=7 Participants
40 Participants
n=5 Participants
49 Participants
n=4 Participants
54 Participants
n=21 Participants
47 Participants
n=8 Participants
277 Participants
n=8 Participants

PRIMARY outcome

Timeframe: Baseline and 16 weeks after the first dose of study medication

Population: Modified Intent-to-Treat: Subjects who took ≥1 dose of randomized study medication and had ≥1 post-Baseline value for HbA1c collected ≤1 week after discontinuing study medication and prior to administration of any new anti-diabetic medication with timing and/or dosage that may have reasonably influenced any subsequent glycemic data collected.

Outcome measures

Outcome measures
Measure
600 mg Met DR qAM
n=88 Participants
600 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
900 mg Met DR qAM
n=93 Participants
900 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1200 mg Met DR qAM
n=88 Participants
1200 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1500 mg Met DR qAM
n=94 Participants
1500 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
Placebo
n=90 Participants
placebo match for 600 and 1200 mg Met DR qAM treatment groups (Placebo 1) and placebo match for 900 and 1500 mg Met DR qAM treatment groups (Placebo 2) Placebo
2000 mg Met IR
n=89 Participants
1000 mg metformin immediate-release twice daily Met IR: metformin immediate-release tablets
Change in HbA1c (%) at 16 Weeks
-0.33 % glycated haemoglobin
Standard Error 0.129
-0.40 % glycated haemoglobin
Standard Error 0.123
-0.49 % glycated haemoglobin
Standard Error 0.129
-0.62 % glycated haemoglobin
Standard Error 0.124
-0.06 % glycated haemoglobin
Standard Error 0.131
-1.10 % glycated haemoglobin
Standard Error 0.129

Adverse Events

600 mg Met DR qAM

Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths

900 mg Met DR qAM

Serious events: 0 serious events
Other events: 24 other events
Deaths: 0 deaths

1200 mg Met DR qAM

Serious events: 4 serious events
Other events: 19 other events
Deaths: 0 deaths

1500 mg Met DR qAM

Serious events: 1 serious events
Other events: 20 other events
Deaths: 0 deaths

Placebo

Serious events: 4 serious events
Other events: 17 other events
Deaths: 1 deaths

2000 mg Met IR

Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
600 mg Met DR qAM
n=94 participants at risk
600 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
900 mg Met DR qAM
n=95 participants at risk
900 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1200 mg Met DR qAM
n=96 participants at risk
1200 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1500 mg Met DR qAM
n=96 participants at risk
1500 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
Placebo
n=96 participants at risk
placebo match for 600 and 1200 mg Met DR qAM treatment groups (Placebo 1) and placebo match for 900 and 1500 mg Met DR qAM treatment groups (Placebo 2) Placebo
2000 mg Met IR
n=94 participants at risk
1000 mg metformin immediate-release twice daily Met IR: metformin immediate-release tablets
Gastrointestinal disorders
Colitis ischaemic
0.00%
0/94 • 16 Weeks
0.00%
0/95 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
1.0%
1/96 • 16 Weeks
0.00%
0/94 • 16 Weeks
Gastrointestinal disorders
Gastrooesophageal reflux disease
0.00%
0/94 • 16 Weeks
0.00%
0/95 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
1.1%
1/94 • 16 Weeks
General disorders
Death
0.00%
0/94 • 16 Weeks
0.00%
0/95 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
1.0%
1/96 • 16 Weeks
0.00%
0/94 • 16 Weeks
Infections and infestations
Arthritis bacterial
0.00%
0/94 • 16 Weeks
0.00%
0/95 • 16 Weeks
1.0%
1/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/94 • 16 Weeks
Infections and infestations
Osteomyelitis
0.00%
0/94 • 16 Weeks
0.00%
0/95 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
1.0%
1/96 • 16 Weeks
0.00%
0/94 • 16 Weeks
Infections and infestations
Pelvic inflammatory disease
0.00%
0/94 • 16 Weeks
0.00%
0/95 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
1.0%
1/96 • 16 Weeks
0.00%
0/94 • 16 Weeks
Metabolism and nutrition disorders
Obesity
0.00%
0/94 • 16 Weeks
0.00%
0/95 • 16 Weeks
1.0%
1/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/94 • 16 Weeks
Musculoskeletal and connective tissue disorders
Arthritis
0.00%
0/94 • 16 Weeks
0.00%
0/95 • 16 Weeks
0.00%
0/96 • 16 Weeks
1.0%
1/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/94 • 16 Weeks
Musculoskeletal and connective tissue disorders
Pain in extremity
0.00%
0/94 • 16 Weeks
0.00%
0/95 • 16 Weeks
1.0%
1/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/94 • 16 Weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
0.00%
0/94 • 16 Weeks
0.00%
0/95 • 16 Weeks
1.0%
1/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/94 • 16 Weeks
Skin and subcutaneous tissue disorders
Hidradenitis
1.1%
1/94 • 16 Weeks
0.00%
0/95 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/94 • 16 Weeks

Other adverse events

Other adverse events
Measure
600 mg Met DR qAM
n=94 participants at risk
600 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
900 mg Met DR qAM
n=95 participants at risk
900 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1200 mg Met DR qAM
n=96 participants at risk
1200 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
1500 mg Met DR qAM
n=96 participants at risk
1500 mg metformin delayed-release once daily in the morning Met DR: metformin delayed-release tablets
Placebo
n=96 participants at risk
placebo match for 600 and 1200 mg Met DR qAM treatment groups (Placebo 1) and placebo match for 900 and 1500 mg Met DR qAM treatment groups (Placebo 2) Placebo
2000 mg Met IR
n=94 participants at risk
1000 mg metformin immediate-release twice daily Met IR: metformin immediate-release tablets
Gastrointestinal disorders
Diarrhoea
7.4%
7/94 • 16 Weeks
7.4%
7/95 • 16 Weeks
11.5%
11/96 • 16 Weeks
11.5%
11/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
13.8%
13/94 • 16 Weeks
Metabolism and nutrition disorders
Hyperglycemia
8.5%
8/94 • 16 Weeks
10.5%
10/95 • 16 Weeks
7.3%
7/96 • 16 Weeks
8.3%
8/96 • 16 Weeks
10.4%
10/96 • 16 Weeks
5.3%
5/94 • 16 Weeks
Gastrointestinal disorders
Nausea
3.2%
3/94 • 16 Weeks
3.2%
3/95 • 16 Weeks
1.0%
1/96 • 16 Weeks
3.1%
3/96 • 16 Weeks
1.0%
1/96 • 16 Weeks
9.6%
9/94 • 16 Weeks
Infections and infestations
Upper respiratory tract infection
1.1%
1/94 • 16 Weeks
5.3%
5/95 • 16 Weeks
1.0%
1/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
2.1%
2/96 • 16 Weeks
2.1%
2/94 • 16 Weeks
Metabolism and nutrition disorders
Worsening Type 2 diabetes mellitus
3.2%
3/94 • 16 Weeks
1.1%
1/95 • 16 Weeks
0.00%
0/96 • 16 Weeks
0.00%
0/96 • 16 Weeks
5.2%
5/96 • 16 Weeks
0.00%
0/94 • 16 Weeks

Additional Information

Chief Scientific Officer

Elcelyx Therapeutics, Inc

Phone: 858-876-1814

Results disclosure agreements

  • Principal investigator is a sponsor employee The results of the Study may be published by INSTITUTE, however the publication shall not disclose any SPONSOR Confidential Information, the INSTITUTE shall send the SPONSOR a copy of any such proposed publication 90 days prior to submission for publication, the INSTITUTE, on request of the SPONSOR, shall delete any SPONSOR Confidential Information in the proposed publication, and the INSTITUTE shall, on the SPONSOR's request, delay submission while the SPONSOR files applications for patents.
  • Publication restrictions are in place

Restriction type: OTHER