Trial Outcomes & Findings for Assessing the PK and Effect on Glucose and GI Hormone Concentrations of Metformin Delayed-Release in Subjects With T2DM (NCT NCT01677299)

Last Updated: 2016-09-20

Results Overview

Measures from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration. The dose of study medication was administered at t = -1 min relative to the start time of the standardized breakfast.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Time points at which data were collected to create the area under the curve (0-t) for plasma metformin were: t = -0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 11 h relative to the start time of the standardized breakfast.

Results posted on

2016-09-20

Participant Flow

Participant milestones

Participant milestones
Measure	Sequence 1: BCAD BID Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)	Sequence 2: ABDC BID Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)	Sequence 3: CDBA BID Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)	Sequence 4: DACB BID Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)
Overall Study STARTED	6	6	6	6
Overall Study COMPLETED	6	3	5	5
Overall Study NOT COMPLETED	0	3	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1: BCAD BID Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)	Sequence 2: ABDC BID Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)	Sequence 3: CDBA BID Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)	Sequence 4: DACB BID Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)
Overall Study Adverse Event	0	2	1	0
Overall Study Withdrawal by Subject	0	1	0	1

Baseline Characteristics

Assessing the PK and Effect on Glucose and GI Hormone Concentrations of Metformin Delayed-Release in Subjects With T2DM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence BCAD n=6 Participants A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID	Sequence ABDC n=6 Participants A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID	Sequence CDBA n=6 Participants A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID	Sequence DACB n=6 Participants A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID	Total n=24 Participants Total of all reporting groups
Age, Continuous	43.2 years STANDARD_DEVIATION 3.54 • n=5 Participants	56.8 years STANDARD_DEVIATION 7.22 • n=7 Participants	49.7 years STANDARD_DEVIATION 13.92 • n=5 Participants	55.3 years STANDARD_DEVIATION 7.79 • n=4 Participants	51.3 years STANDARD_DEVIATION 9.98 • n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	12 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	12 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	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
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	19 Participants n=21 Participants
Race (NIH/OMB) More than one race	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
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	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	2 Participants n=4 Participants	14 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	10 Participants n=21 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
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	6 participants n=4 Participants	24 participants n=21 Participants
BMI	34.13 kg/mˆ2 STANDARD_DEVIATION 5.455 • n=5 Participants	30.67 kg/mˆ2 STANDARD_DEVIATION 2.793 • n=7 Participants	35.65 kg/mˆ2 STANDARD_DEVIATION 2.935 • n=5 Participants	32.87 kg/mˆ2 STANDARD_DEVIATION 3.644 • n=4 Participants	33.33 kg/mˆ2 STANDARD_DEVIATION 4.05 • n=21 Participants
eGFR	117.94 mL/min/1.73 mˆ2 STANDARD_DEVIATION 22.065 • n=5 Participants	114.65 mL/min/1.73 mˆ2 STANDARD_DEVIATION 21.348 • n=7 Participants	107.54 mL/min/1.73 mˆ2 STANDARD_DEVIATION 16.644 • n=5 Participants	93.43 mL/min/1.73 mˆ2 STANDARD_DEVIATION 20.354 • n=4 Participants	108.39 mL/min/1.73 mˆ2 STANDARD_DEVIATION 21.161 • n=21 Participants
HbA1c	7.62 % STANDARD_DEVIATION 1.234 • n=5 Participants	7.33 % STANDARD_DEVIATION 0.965 • n=7 Participants	8.07 % STANDARD_DEVIATION 1.102 • n=5 Participants	6.37 % STANDARD_DEVIATION .339 • n=4 Participants	7.35 % STANDARD_DEVIATION 1.108 • n=21 Participants
FPG	182.5 mg/dL STANDARD_DEVIATION 71.55 • n=5 Participants	158 mg/dL STANDARD_DEVIATION 42.96 • n=7 Participants	179 mg/dL STANDARD_DEVIATION 69.59 • n=5 Participants	124.3 mg/dL STANDARD_DEVIATION 15.03 • n=4 Participants	161 mg/dL STANDARD_DEVIATION 56.34 • n=21 Participants

PRIMARY outcome

Timeframe: Time points at which data were collected to create the area under the curve (0-t) for plasma metformin were: t = -0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 11 h relative to the start time of the standardized breakfast.

Population: Evaluable Population

Outcome measures

Outcome measures
Measure	1000 mg EFB0026 n=19 Participants BID	1000 mg EFB0027 n=19 Participants BID	500 mg EFB0027 n=19 Participants BID	500 mg EFB0026 + 1000 mg EFB0027 n=19 Participants BID
Area Under the Curve (0-t) of Plasma Metformin	8672 ng*h/mL Standard Deviation 29.7	4774 ng*h/mL Standard Deviation 29.9	3842 ng*h/mL Standard Deviation 37.6	8075 ng*h/mL Standard Deviation 38.6

PRIMARY outcome

Timeframe: Change from Baseline (Day 1) to Day 5

Population: Evaluable Population

LS mean difference from Baseline (Day 1) to Day 5

Outcome measures

Outcome measures
Measure	1000 mg EFB0026 n=19 Participants BID	1000 mg EFB0027 n=19 Participants BID	500 mg EFB0027 n=19 Participants BID	500 mg EFB0026 + 1000 mg EFB0027 n=19 Participants BID
Change in Fasting Plasma Glucose	-22.5 mg/dL Standard Error 6.8	-19.9 mg/dL Standard Error 5	-16.4 mg/dL Standard Error 3.8	-21.2 mg/dL Standard Error 4.7

PRIMARY outcome

Timeframe: Ratio of Day 5 to Baseline

Population: Evaluable

Outcome measures

Outcome measures
Measure	1000 mg EFB0026 n=19 Participants BID	1000 mg EFB0027 n=19 Participants BID	500 mg EFB0027 n=19 Participants BID	500 mg EFB0026 + 1000 mg EFB0027 n=19 Participants BID
Within Treatment Comparison Based on Ratios of AUCs of GLP-1	1.87 none (values are ratios) Standard Error 0.18	1.62 none (values are ratios) Standard Error .11	1.69 none (values are ratios) Standard Error .15	1.88 none (values are ratios) Standard Error .19

PRIMARY outcome

Timeframe: Ratio of Day 5 to Baseline

Population: Evaluable Population

Outcome measures

Outcome measures
Measure	1000 mg EFB0026 n=19 Participants BID	1000 mg EFB0027 n=19 Participants BID	500 mg EFB0027 n=19 Participants BID	500 mg EFB0026 + 1000 mg EFB0027 n=19 Participants BID
Within Treatment Comparison Based on Ratios of AUCs of PYY	1.55 none (values are ratios) Standard Error .09	1.38 none (values are ratios) Standard Error .09	1.46 none (values are ratios) Standard Error .06	1.49 none (values are ratios) Standard Error .06

Adverse Events

1000 mg EFB0026 BID

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

1000 mg EFB0027 BID

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

500 mg EFB0027 BID

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

500 mg EFB0026 BID Plus 1000 mg EFB0027 BID

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1000 mg EFB0026 BID n=22 participants at risk A: Metformin immediate release BID	1000 mg EFB0027 BID n=20 participants at risk B: Metformin delayed release BID	500 mg EFB0027 BID n=20 participants at risk C: Metformin delayed release BID	500 mg EFB0026 BID Plus 1000 mg EFB0027 BID n=21 participants at risk D: Metformin immediate plus Metformin delayed release
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal Stromal Tumour	0.00% 0/22 Population Intent to treat (ITT)	5.0% 1/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/21 Population Intent to treat (ITT)

Other adverse events

Additional Information

Senior Director, Development

Elcelyx Therapeutics, Inc

Phone: 858-876-1814

Email: [email protected]

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

Measure	1000 mg EFB0026 BID n=22 participants at risk A: Metformin immediate release BID	1000 mg EFB0027 BID n=20 participants at risk B: Metformin delayed release BID	500 mg EFB0027 BID n=20 participants at risk C: Metformin delayed release BID	500 mg EFB0026 BID Plus 1000 mg EFB0027 BID n=21 participants at risk D: Metformin immediate plus Metformin delayed release
Gastrointestinal disorders Abdominal Discomfort	0.00% 0/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	4.8% 1/21 Population Intent to treat (ITT)
Gastrointestinal disorders Abdominal Distension	0.00% 0/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	4.8% 1/21 Population Intent to treat (ITT)
Gastrointestinal disorders Abdominal Pain	0.00% 0/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	5.0% 1/20 Population Intent to treat (ITT)	4.8% 1/21 Population Intent to treat (ITT)
Gastrointestinal disorders Diarrhoea	13.6% 3/22 Population Intent to treat (ITT)	15.0% 3/20 Population Intent to treat (ITT)	10.0% 2/20 Population Intent to treat (ITT)	33.3% 7/21 Population Intent to treat (ITT)
Gastrointestinal disorders Dyspepsia	4.5% 1/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	5.0% 1/20 Population Intent to treat (ITT)	4.8% 1/21 Population Intent to treat (ITT)
Gastrointestinal disorders Frequent Bowel Movements	0.00% 0/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	4.8% 1/21 Population Intent to treat (ITT)
Gastrointestinal disorders Nausea	9.1% 2/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	14.3% 3/21 Population Intent to treat (ITT)
Gastrointestinal disorders Retching	4.5% 1/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/21 Population Intent to treat (ITT)
Gastrointestinal disorders Vomiting	9.1% 2/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/21 Population Intent to treat (ITT)
General disorders Fatigue	0.00% 0/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	5.0% 1/20 Population Intent to treat (ITT)	0.00% 0/21 Population Intent to treat (ITT)
Infections and infestations Oral Herpes	0.00% 0/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	4.8% 1/21 Population Intent to treat (ITT)
Investigations Weight Decreased	0.00% 0/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	4.8% 1/21 Population Intent to treat (ITT)
Musculoskeletal and connective tissue disorders Pain in Extremity	0.00% 0/22 Population Intent to treat (ITT)	5.0% 1/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/21 Population Intent to treat (ITT)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal Stromal Tumor	0.00% 0/22 Population Intent to treat (ITT)	5.0% 1/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/21 Population Intent to treat (ITT)
Nervous system disorders Dizziness	13.6% 3/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/21 Population Intent to treat (ITT)
Nervous system disorders Headache	9.1% 2/22 Population Intent to treat (ITT)	5.0% 1/20 Population Intent to treat (ITT)	5.0% 1/20 Population Intent to treat (ITT)	0.00% 0/21 Population Intent to treat (ITT)
Nervous system disorders Sinus Headache	4.5% 1/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/21 Population Intent to treat (ITT)
Renal and urinary disorders Pollakiuria	0.00% 0/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	4.8% 1/21 Population Intent to treat (ITT)
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/22 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	0.00% 0/20 Population Intent to treat (ITT)	4.8% 1/21 Population Intent to treat (ITT)