Trial Outcomes & Findings for Study Evaluating Safety, Tolerability, And Action Of OAP-189 In Subjects With Type 2 Diabetes On Metformin (NCT NCT00970593)

NCT ID: NCT00970593

Last Updated: 2020-11-02

Results Overview

Physical examination included examination of skin, head, eyes, ears, nose, throat (HEENT), heart, lungs, abdomen, extremities, neurological function, back and lymph nodes. Clinically significant physical examination abnormalities were considered as adverse events based on investigator's discretion.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 92 participants
• Primary outcome timeframe: Baseline up to 17 days after last dose of study drug (Day 31)
• Results posted on: 2020-11-02

Participant Flow

All participants received the background metformin immediate release tablets, during the 4 weeks run-in period. Compliant participants were then randomized to study treatments for a maximum period of 31 days.

Participant milestones

Measure	OAP-189 0.2 mg IR Participants received OAP-189 0.2 milligram (mg), immediate release (IR) infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg Participants received OAP-189 0.9 mg, modified release (MR) infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Overall Study STARTED	11	15	13	12	20	5	16
Overall Study COMPLETED	10	14	7	12	20	5	14
Overall Study NOT COMPLETED	1	1	6	0	0	0	2

Reasons for withdrawal

Measure	OAP-189 0.2 mg IR Participants received OAP-189 0.2 milligram (mg), immediate release (IR) infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg Participants received OAP-189 0.9 mg, modified release (MR) infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Overall Study Adverse Event	1	1	0	0	0	0	0
Overall Study Discontinuation of study by sponsor	0	0	5	0	0	0	2
Overall Study Withdrawal by Subject	0	0	1	0	0	0	0

Baseline Characteristics

Study Evaluating Safety, Tolerability, And Action Of OAP-189 In Subjects With Type 2 Diabetes On Metformin

Baseline characteristics by cohort

Measure	OAP-189 0.2 mg IR n=11 Participants Participants received OAP-189 0.2 milligram (mg), immediate release (IR) infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=15 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=13 Participants Participants received OAP-189 0.9 mg, modified release (MR) infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=12 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=20 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR n=5 Participants Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR n=16 Participants Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Total n=92 Participants Total of all reporting groups
Age, Continuous	55.00 years STANDARD_DEVIATION 8.65 • n=5 Participants	53.60 years STANDARD_DEVIATION 6.33 • n=7 Participants	52.69 years STANDARD_DEVIATION 3.12 • n=5 Participants	54.92 years STANDARD_DEVIATION 6.69 • n=4 Participants	51.50 years STANDARD_DEVIATION 9.64 • n=21 Participants	53.80 years STANDARD_DEVIATION 9.34 • n=10 Participants	54.75 years STANDARD_DEVIATION 6.83 • n=115 Participants	53.57 years STANDARD_DEVIATION 7.33 • n=24 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants	2 Participants n=10 Participants	6 Participants n=115 Participants	26 Participants n=24 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	8 Participants n=4 Participants	16 Participants n=21 Participants	3 Participants n=10 Participants	10 Participants n=115 Participants	66 Participants n=24 Participants

PRIMARY outcome

Timeframe: Baseline up to 17 days after last dose of study drug (Day 31)

Population: Safety population included all randomly assigned participants who received at least 1 dose of study medication.

Physical examination included examination of skin, head, eyes, ears, nose, throat (HEENT), heart, lungs, abdomen, extremities, neurological function, back and lymph nodes. Clinically significant physical examination abnormalities were considered as adverse events based on investigator's discretion.

Outcome measures

Measure	OAP-189 0.2 mg IR n=11 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=15 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=13 Participants Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=12 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=20 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR n=5 Participants Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR n=16 Participants Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Number of Participants With Clinically Significant Physical Examination Abnormalities	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline up to 17 days after last dose of study drug (Day 31)

Population: Safety population included all randomly assigned participants who received at least 1 dose of study medication.

Criteria for clinically significant vital sign abnormalities: sitting systolic blood pressure (SBP) of (greater than equal to) >=160 millimeter of mercury (mmHg), (less than equal to) <=90 mmHg, >=20 mmHg increase and decrease from baseline; sitting diastolic blood pressure (DBP) of >=100 mmHg, <=50 mmHg, >=15 mmHg increase and decrease from baseline; heart rate of >=120 beats per minute (bpm), <=45 bpm, (greater than) >15 bpm increase and decrease from baseline, orthostatic SBP: decrease of >=20 mm Hg from sitting value, orthostatic DBP: decrease of >=20 mm Hg from sitting value, orthostatic heart rate: increase of >=30 bpm from sitting value, oral temperature of (less than) <35 or >38.3 degree celsius, respiratory rate of <10 or >25 breaths per minute, weight: maximum increase or decrease of >=7 percent (%) from baseline.

Outcome measures

Measure	OAP-189 0.2 mg IR n=11 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=15 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=13 Participants Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=12 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=20 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR n=5 Participants Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR n=16 Participants Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Number of Participants With Clinically Significant Vital Signs Abnormalities	1 participants	2 participants	1 participants	2 participants	4 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: Baseline up to 17 days after last dose of study drug (Day 31)

Population: Safety population included all randomly assigned participants who received at least 1 dose of study medication. Here, 'N' (Number of Participants analyzed) signifies those participants who were evaluable for this measure.

Criteria for clinically significant ECG abnormalities: PR interval >=220 millisecond (msec) or a change of >=20 msec from baseline values, QRS interval >=120 msec, QTc interval >450 msec (in males) and >470 msec (in females).

Outcome measures

Measure	OAP-189 0.2 mg IR n=11 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=15 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=8 Participants Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=12 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=20 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR n=5 Participants Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR n=14 Participants Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities	0 participants	0 participants	2 participants	4 participants	4 participants	0 participants	7 participants

PRIMARY outcome

Timeframe: Baseline up to 17 days after last dose of study drug (Day 31)

Population: Safety population included all randomly assigned participants who received at least 1 dose of study medication.

Hematocrit, haemoglobin: decrease of >=0.05 L/L and >=20 g/L from baseline respectively, WBC count:<3*10^9 /L, neutrophils: <1.5*10^9 /L, platelet count: <100*10^9 /L, eosinophil: <0.5*10^9 /L; prothrombin time, partial thromboplastin time >1.5*upper limit of normal (ULN); sodium:>5 mmol/L above ULN or below lower limit of normal(LLN), potassium >0.5 mmol/L above ULN or below LLN, creatinine >1.36*ULN, blood urea nitrogen >1.5*ULN, glucose (fasting) >0.83 mmol/L above ULN or below LLN, glucose (non-fasting) >5 mmol/L above ULN or >0.56 below LLN, calcium, magnesium: Change of >=0.25 and >=0.21 mmol/L from baseline respectively, phosphorus >0.162 mmol/L above ULN or below LLN, total protein, albumin, uric acid: change of >=20g/L, >=10 g/L, >0.119 mmol/L from baseline respectively, creatinine kinase >3*ULN, total cholesterol >7.77 mmol/L, triglycerides >3.39 mmol/L: AST, ALT, total bilirubin >2*ULN, alkaline phosphatase >1.5*ULN, alpha-glumatyl transferase, lactate dehydrogenase >3*ULN.

Outcome measures

Measure	OAP-189 0.2 mg IR n=11 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=15 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=13 Participants Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=12 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=20 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR n=5 Participants Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR n=16 Participants Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Number of Participants With Clinically Significant Laboratory Abnormalities	10 participants	15 participants	13 participants	9 participants	19 participants	5 participants	15 participants

PRIMARY outcome

Timeframe: Baseline up to 17 days after last dose of study drug (Day 31)

Population: Safety population included all randomly assigned participants who received at least 1 dose of study medication.

Injection site reactions included irritation, erythema, pain, hematoma, inflammation.

Outcome measures

Measure	OAP-189 0.2 mg IR n=11 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=15 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=13 Participants Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=12 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=20 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR n=5 Participants Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR n=16 Participants Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Number of Participants With Injection Site Reactions Irritation	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	1 participants
Number of Participants With Injection Site Reactions Erythema	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	1 participants
Number of Participants With Injection Site Reactions Pain	0 participants	0 participants	0 participants	2 participants	1 participants	0 participants	0 participants
Number of Participants With Injection Site Reactions Hematoma	0 participants	0 participants	0 participants	0 participants	3 participants	0 participants	1 participants
Number of Participants With Injection Site Reactions Inflammation	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: Baseline up to 17 days after last dose of study drug (Day 31)

Population: Safety population included all randomly assigned participants who received at least 1 dose of study medication.

Criteria: Blood glucose levels >15 milligram per deciliter (mg/dL) above ULN or >15 mg/dL below LLN.

Outcome measures

Measure	OAP-189 0.2 mg IR n=11 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=15 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=13 Participants Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=12 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=20 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR n=5 Participants Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR n=16 Participants Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Number of Participants With Clinically Significant Fasting Glucose Level Abnormalities	10 participants	15 participants	13 participants	9 participants	19 participants	5 participants	15 participants

PRIMARY outcome

Timeframe: Baseline up to 17 days after last dose of study drug (Day 31)

Population: Safety population included all randomly assigned participants who received at least 1 dose of study medication.

Hypoglycaemia is a condition characterized by abnormally low blood glucose (blood sugar) levels, usually <=50 mg/dL.

Outcome measures

Measure	OAP-189 0.2 mg IR n=11 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=15 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=13 Participants Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=12 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=20 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR n=5 Participants Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR n=16 Participants Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Number of Participants With Hypoglycaemia	0 participants	0 participants	0 participants	2 participants	1 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline up to 17 days after last dose of study drug (Day 31)

Population: Safety population included all randomly assigned participants who received at least 1 dose of study medication.

Criteria for drug induced liver injury: Levels of aspartate transaminase (AST) or alanine transaminase (ALT) should be >= 3 times ULN concurrent with a total bilirubin of >=2 times ULN with no evidence of hemolysis and an alkaline phosphatase should be <=2 times ULN.

Outcome measures

Measure	OAP-189 0.2 mg IR n=11 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=15 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=13 Participants Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=12 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=20 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR n=5 Participants Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR n=16 Participants Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Number of Participants With Drug-Induced Liver Injury	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline, Day 8

Population: Safety population included all randomly assigned participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable at specified time points. This outcome measure was not to be analyzed in participants of OAP-189 0.2, 0.4 mg IR and Placebo IR as pre-specified in the protocol.

Fasting glucose levels were determined before administration of OAP-189 using a glucometer.

Outcome measures

Measure	OAP-189 0.2 mg IR n=13 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=12 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=20 Participants Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=16 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Change From Baseline in Predose Fasting Glucose Levels at Day 8 Baseline	10.02 millimole per liter Standard Deviation 2.373	10.06 millimole per liter Standard Deviation 2.583	9.27 millimole per liter Standard Deviation 2.148	9.01 millimole per liter Standard Deviation 1.769	—	—	—
Change From Baseline in Predose Fasting Glucose Levels at Day 8 Change at Day 8	-1.37 millimole per liter Standard Deviation 2.222	-2.75 millimole per liter Standard Deviation 1.663	-2.47 millimole per liter Standard Deviation 1.400	-0.25 millimole per liter Standard Deviation 1.166	—	—	—

PRIMARY outcome

Timeframe: Baseline, Day 15

Population: Safety population included all randomly assigned participants who received at least 1 dose of study medication. Here, 'N' signifies those participants who were evaluable for this measure. This outcome measure was not to be analyzed in participants of OAP-189 0.2, 0.4 mg IR and Placebo IR as pre-specified in protocol.

Fasting glucose levels were determined before administration of OAP-189 using a glucometer.

Outcome measures

Measure	OAP-189 0.2 mg IR n=7 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=12 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=20 Participants Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=14 Participants Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Change From Baseline in Predose Fasting Glucose Levels at Day 15	-2.62 millimole per liter Standard Deviation 0.998	-3.87 millimole per liter Standard Deviation 1.783	-3.49 millimole per liter Standard Deviation 1.643	-0.33 millimole per liter Standard Deviation 1.273	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6 hours post-dose on Day 14

Population: Pharmacokinetic (PK) analysis set. Here, 'N' (Number of Participants analyzed) signifies those participants who were evaluable for this measure. This outcome measure was not to be analyzed in participants of OAP-189 0.2, 0.4 mg IR, Placebo IR, OAP-189 MR (0.25:1 Z/P ratio) 1.2 mg followed by 1.6 mg and Placebo MR as pre-specified in protocol.

Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ =2 nanogram per millliter) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.

Outcome measures

Measure	OAP-189 0.2 mg IR n=7 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=12 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Plasma Concentration Versus Time Summary of Metformin Following Single Dose of OAP-189 Pre-dose	318.7 nanogram per milliliter Standard Deviation 140.36	455.6 nanogram per milliliter Standard Deviation 246.43	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Single Dose of OAP-189 1 hour post dose	899.1 nanogram per milliliter Standard Deviation 344.02	990.9 nanogram per milliliter Standard Deviation 453.01	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Single Dose of OAP-189 2 hour post dose	885.4 nanogram per milliliter Standard Deviation 364.20	1112 nanogram per milliliter Standard Deviation 652.61	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Single Dose of OAP-189 3 hour post dose	881.4 nanogram per milliliter Standard Deviation 357.83	1063 nanogram per milliliter Standard Deviation 613.86	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Single Dose of OAP-189 4 hour post dose	912.3 nanogram per milliliter Standard Deviation 381.22	943.7 nanogram per milliliter Standard Deviation 474.35	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Single Dose of OAP-189 6 hour post dose	869.7 nanogram per milliliter Standard Deviation 215.27	804.8 nanogram per milliliter Standard Deviation 349.20	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 hours post-dose on Day 7

Population: PK analysis set. Here, 'N' = participants evaluable for this measure. This outcome was not to be analyzed in participants of Placebo IR, OAP-189 MR (0.05:1 Z/P ratio) 0.9 mg followed by 1.2 mg, OAP-189 MR (0.1:1 Z/P ratio) 1.2 mg followed by 1.6 mg, OAP-189 MR (0.25:1 Z/P ratio) 1.2 mg followed by 1.6 mg and Placebo MR as pre-specified in protocol.

Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ =2 nanogram per millliter) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.

Outcome measures

Measure	OAP-189 0.2 mg IR n=10 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=14 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 Pre-dose	544.7 nanogram per milliliter Standard Deviation 334.72	558.9 nanogram per milliliter Standard Deviation 386.19	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 1 hour post dose	998.8 nanogram per milliliter Standard Deviation 360.42	1276 nanogram per milliliter Standard Deviation 858.80	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 2 hour post dose	980.7 nanogram per milliliter Standard Deviation 336.37	1084 nanogram per milliliter Standard Deviation 582.26	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 3 hour post dose	995.8 nanogram per milliliter Standard Deviation 342.21	985.5 nanogram per milliliter Standard Deviation 424.50	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 4 hour post dose	938.3 nanogram per milliliter Standard Deviation 355.38	974.7 nanogram per milliliter Standard Deviation 504.81	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 6 hour post dose	804.6 nanogram per milliliter Standard Deviation 343.23	854.0 nanogram per milliliter Standard Deviation 415.21	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 8 hour post dose	617.0 nanogram per milliliter Standard Deviation 265.18	735.4 nanogram per milliliter Standard Deviation 350.03	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 10 hour post dose	462.4 nanogram per milliliter Standard Deviation 194.50	658.1 nanogram per milliliter Standard Deviation 457.83	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 12 hour post dose	987.2 nanogram per milliliter Standard Deviation 442.22	1029 nanogram per milliliter Standard Deviation 477.30	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 14 hour post dose	972.6 nanogram per milliliter Standard Deviation 415.05	976.4 nanogram per milliliter Standard Deviation 497.10	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 16 hour post dose	889.7 nanogram per milliliter Standard Deviation 465.26	906.1 nanogram per milliliter Standard Deviation 418.88	—	—	—	—	—
Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 24 hour post dose	455.1 nanogram per milliliter Standard Deviation 488.53	503.5 nanogram per milliliter Standard Deviation 334.27	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose (2 hours before dosing), 2, 4, 6 hours post-dose on Day 7; Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 48, 72 hours post-dose on Day 14

Population: PK analysis set. Here, 'n' signifies those participants who were evaluable at specified time points. This outcome measure was not to be analyzed in participants of OAP-189 0.2, 0.4 mg IR, Placebo IR and MR as pre-specified in protocol.

Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ = 0.500 nanogram per millliter) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.

Outcome measures

Measure	OAP-189 0.2 mg IR n=13 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=12 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=20 Participants Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 7: Pre-dose	2.173 nanogram per milliliter Standard Deviation 0.55480	3.253 nanogram per milliliter Standard Deviation 1.2371	2.313 nanogram per milliliter Standard Deviation 1.0927	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 7: 2 hour post dose	8.065 nanogram per milliliter Standard Deviation 2.8023	11.56 nanogram per milliliter Standard Deviation 8.9549	5.380 nanogram per milliliter Standard Deviation 3.2235	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 7: 4 hour post dose	10.40 nanogram per milliliter Standard Deviation 4.8907	14.21 nanogram per milliliter Standard Deviation 10.429	6.113 nanogram per milliliter Standard Deviation 2.8196	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 7: 6 hour post dose	9.173 nanogram per milliliter Standard Deviation 4.4176	11.71 nanogram per milliliter Standard Deviation 6.7732	5.249 nanogram per milliliter Standard Deviation 2.7225	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: Pre-dose	3.350 nanogram per milliliter Standard Deviation 0.85499	4.550 nanogram per milliliter Standard Deviation 2.0888	3.404 nanogram per milliliter Standard Deviation 1.6691	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 1 hour post dose	6.740 nanogram per milliliter Standard Deviation 3.4367	18.46 nanogram per milliliter Standard Deviation 34.903	7.686 nanogram per milliliter Standard Deviation 5.0265	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 2 hour post dose	9.747 nanogram per milliliter Standard Deviation 4.8634	19.53 nanogram per milliliter Standard Deviation 23.410	8.492 nanogram per milliliter Standard Deviation 4.0211	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 3 hour post dose	11.23 nanogram per milliliter Standard Deviation 4.4618	19.79 nanogram per milliliter Standard Deviation 17.035	8.969 nanogram per milliliter Standard Deviation 3.6809	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 4 hour post dose	11.70 nanogram per milliliter Standard Deviation 4.4452	17.88 nanogram per milliliter Standard Deviation 12.785	8.911 nanogram per milliliter Standard Deviation 3.5977	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 6 hour post dose	9.611 nanogram per milliliter Standard Deviation 3.7471	14.97 nanogram per milliliter Standard Deviation 10.234	7.353 nanogram per milliliter Standard Deviation 3.2211	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 8 hour post dose	8.094 nanogram per milliliter Standard Deviation 3.3158	12.83 nanogram per milliliter Standard Deviation 7.6125	6.326 nanogram per milliliter Standard Deviation 2.7418	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 10 hour post dose (	6.991 nanogram per milliliter Standard Deviation 2.6902	10.13 nanogram per milliliter Standard Deviation 5.8597	5.845 nanogram per milliliter Standard Deviation 2.1174	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 12 hour post dose	5.431 nanogram per milliliter Standard Deviation 2.0067	7.939 nanogram per milliliter Standard Deviation 4.6575	5.152 nanogram per milliliter Standard Deviation 2.3713	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 14 hour post dose	4.341 nanogram per milliliter Standard Deviation 1.5433	6.708 nanogram per milliliter Standard Deviation 3.4394	4.604 nanogram per milliliter Standard Deviation 1.7001	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 16 hour post dose	4.160 nanogram per milliliter Standard Deviation 0.93113	5.993 nanogram per milliliter Standard Deviation 3.0649	4.612 nanogram per milliliter Standard Deviation 1.8386	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 24 hour post dose	2.910 nanogram per milliliter Standard Deviation 0.70512	3.911 nanogram per milliliter Standard Deviation 1.7983	3.688 nanogram per milliliter Standard Deviation 1.2721	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 48 hour post dose	1.285 nanogram per milliliter Standard Deviation 0.29853	1.781 nanogram per milliliter Standard Deviation 1.1929	1.968 nanogram per milliliter Standard Deviation 1.1127	—	—	—	—
Plasma Concentration Versus Time Summary of Single Dose of OAP-189 Day 14: 72 hour post dose	0.4900 nanogram per milliliter Standard Deviation 0.43025	1.070 nanogram per milliliter Standard Deviation 1.5187	0.8378 nanogram per milliliter Standard Deviation 0.72049	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 hours post-dose on Day 7

Population: PK analysis set. Here, 'N' = participants evaluable for this measure. This outcome was not to be analyzed in participants of Placebo IR, OAP-189 MR (0.05:1 Z/P ratio) 0.9 mg followed by 1.2 mg, OAP-189 MR (0.1:1 Z/P ratio) 1.2 mg followed by 1.6 mg, OAP-189 MR (0.25:1 Z/P ratio) 1.2 mg followed by 1.6 mg and Placebo MR as pre-specified in protocol.

Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLOQ =0.500 nanogram per millliter) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) =0.

Outcome measures

Measure	OAP-189 0.2 mg IR n=10 Participants Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=14 Participants Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 Pre-dose	1.667 nanogram per milliliter Standard Deviation 1.4404	3.548 nanogram per milliliter Standard Deviation 1.9612	—	—	—	—	—
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 1 hour post dose	2.727 nanogram per milliliter Standard Deviation 1.4936	4.920 nanogram per milliliter Standard Deviation 1.7474	—	—	—	—	—
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 2 hour post dose	4.454 nanogram per milliliter Standard Deviation 2.9789	7.824 nanogram per milliliter Standard Deviation 2.9187	—	—	—	—	—
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 3 hour post dose	5.614 nanogram per milliliter Standard Deviation 3.0258	10.09 nanogram per milliliter Standard Deviation 3.9267	—	—	—	—	—
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 4 hour post dose	6.080 nanogram per milliliter Standard Deviation 3.0045	11.79 nanogram per milliliter Standard Deviation 5.0857	—	—	—	—	—
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 6 hour post dose	5.206 nanogram per milliliter Standard Deviation 2.0969	9.204 nanogram per milliliter Standard Deviation 4.3138	—	—	—	—	—
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 8 hour post dose	4.064 nanogram per milliliter Standard Deviation 1.6576	6.889 nanogram per milliliter Standard Deviation 2.7902	—	—	—	—	—
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 10 hour post dose	2.743 nanogram per milliliter Standard Deviation 1.0067	5.076 nanogram per milliliter Standard Deviation 2.0844	—	—	—	—	—
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 12 hour post dose	5.315 nanogram per milliliter Standard Deviation 2.0278	9.376 nanogram per milliliter Standard Deviation 3.7875	—	—	—	—	—
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 14 hour post dose	6.976 nanogram per milliliter Standard Deviation 2.7327	11.61 nanogram per milliliter Standard Deviation 6.2016	—	—	—	—	—
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 16 hour post dose	6.157 nanogram per milliliter Standard Deviation 1.8865	10.87 nanogram per milliliter Standard Deviation 4.9706	—	—	—	—	—
Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 24 hour post dose	1.315 nanogram per milliliter Standard Deviation 0.87065	2.591 nanogram per milliliter Standard Deviation 1.3243	—	—	—	—	—

Adverse Events

OAP-189 0.2 mg IR

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

OAP-189 0.4 mg IR

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo IR

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo MR

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	OAP-189 0.2 mg IR n=11 participants at risk Participants received OAP-189 0.2 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 0.4 mg IR n=15 participants at risk Participants received OAP-189 0.4 mg, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.05:1 Z/P Ratio) 0.9 mg Followed by 1.2 mg n=13 participants at risk Participants received OAP-189 0.9 mg, MR infusion (with 0.05:1 zinc to peptide \[Z/P\] ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.2 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=12 participants at risk Participants received OAP-189 1.2 mg, MR infusion (with 0.1:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	OAP-189 MR (0.25:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg n=20 participants at risk Participants received OAP-189 1.2 mg, MR infusion (with 0.25:1 Z/P ratio) subcutaneously once daily from Day 1 to Day 7 followed by OAP-189 1.6 mg, MR infusion subcutaneously once daily from Day 8 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo IR n=5 participants at risk Participants received placebo matched to OAP-189, IR infusion subcutaneously twice daily from Day 1 to Day 7 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).	Placebo MR n=16 participants at risk Participants received placebo matched to OAP-189, MR infusion subcutaneously once daily from Day 1 to Day 14 along with background metformin 850 mg immediate release tablets or as per standard clinical practice (based on the dose prior to randomization).
Blood and lymphatic system disorders Anaemia	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	6.2% 1/16
Ear and labyrinth disorders Ear pain	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
Ear and labyrinth disorders Tinnitus	0.00% 0/11	0.00% 0/15	15.4% 2/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Eye disorders Vision blurred	0.00% 0/11	6.7% 1/15	0.00% 0/13	8.3% 1/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
Gastrointestinal disorders Abdominal discomfort	0.00% 0/11	0.00% 0/15	15.4% 2/13	25.0% 3/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Gastrointestinal disorders Abdominal distension	0.00% 0/11	13.3% 2/15	30.8% 4/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
Gastrointestinal disorders Abdominal pain	0.00% 0/11	6.7% 1/15	0.00% 0/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
Gastrointestinal disorders Abdominal pain upper	9.1% 1/11	6.7% 1/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Gastrointestinal disorders Constipation	0.00% 0/11	13.3% 2/15	23.1% 3/13	25.0% 3/12	0.00% 0/20	0.00% 0/5	12.5% 2/16
Gastrointestinal disorders Diarrhoea	9.1% 1/11	13.3% 2/15	23.1% 3/13	16.7% 2/12	10.0% 2/20	0.00% 0/5	0.00% 0/16
Gastrointestinal disorders Dry mouth	0.00% 0/11	6.7% 1/15	15.4% 2/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	6.2% 1/16
Gastrointestinal disorders Dyspepsia	0.00% 0/11	6.7% 1/15	38.5% 5/13	0.00% 0/12	10.0% 2/20	0.00% 0/5	0.00% 0/16
Gastrointestinal disorders Eructation	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
Gastrointestinal disorders Flatulence	0.00% 0/11	13.3% 2/15	23.1% 3/13	16.7% 2/12	0.00% 0/20	0.00% 0/5	12.5% 2/16
Gastrointestinal disorders Hyperchlorhydria	0.00% 0/11	0.00% 0/15	0.00% 0/13	8.3% 1/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Gastrointestinal disorders Lip dry	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	6.2% 1/16
Gastrointestinal disorders Nausea	27.3% 3/11	53.3% 8/15	69.2% 9/13	50.0% 6/12	40.0% 8/20	0.00% 0/5	12.5% 2/16
Gastrointestinal disorders Vomiting	9.1% 1/11	53.3% 8/15	15.4% 2/13	41.7% 5/12	20.0% 4/20	0.00% 0/5	12.5% 2/16
Gastrointestinal disorders Vomiting projectile	0.00% 0/11	6.7% 1/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
General disorders Application site irritation	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	6.2% 1/16
General disorders Asthenia	9.1% 1/11	13.3% 2/15	0.00% 0/13	16.7% 2/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
General disorders Chills	0.00% 0/11	6.7% 1/15	7.7% 1/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
General disorders Fatigue	0.00% 0/11	0.00% 0/15	7.7% 1/13	8.3% 1/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
General disorders Inflammation	9.1% 1/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
General disorders Infusion site inflammation	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	6.2% 1/16
General disorders Injection site erythema	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	6.2% 1/16
General disorders Injection site haematoma	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	15.0% 3/20	0.00% 0/5	6.2% 1/16
General disorders Injection site pain	0.00% 0/11	0.00% 0/15	0.00% 0/13	16.7% 2/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
General disorders Injection site reaction	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	10.0% 2/20	0.00% 0/5	0.00% 0/16
General disorders Non-cardiac chest pain	0.00% 0/11	6.7% 1/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
General disorders Pain	9.1% 1/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
General disorders Sluggishness	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
Infections and infestations Otitis externa	0.00% 0/11	0.00% 0/15	7.7% 1/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Injury, poisoning and procedural complications Contusion	0.00% 0/11	0.00% 0/15	7.7% 1/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	6.2% 1/16
Metabolism and nutrition disorders Decreased appetite	0.00% 0/11	20.0% 3/15	23.1% 3/13	33.3% 4/12	10.0% 2/20	0.00% 0/5	0.00% 0/16
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/11	0.00% 0/15	0.00% 0/13	16.7% 2/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
Metabolism and nutrition disorders Polydipsia	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	20.0% 1/5	0.00% 0/16
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/11	0.00% 0/15	15.4% 2/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	6.2% 1/16
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/11	0.00% 0/15	7.7% 1/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Nervous system disorders Dizziness	9.1% 1/11	33.3% 5/15	15.4% 2/13	16.7% 2/12	10.0% 2/20	0.00% 0/5	6.2% 1/16
Nervous system disorders Dysgeusia	0.00% 0/11	0.00% 0/15	7.7% 1/13	8.3% 1/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Nervous system disorders Headache	0.00% 0/11	20.0% 3/15	15.4% 2/13	41.7% 5/12	20.0% 4/20	0.00% 0/5	6.2% 1/16
Nervous system disorders Lethargy	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
Nervous system disorders Somnolence	0.00% 0/11	0.00% 0/15	0.00% 0/13	8.3% 1/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Nervous system disorders Tremor	0.00% 0/11	0.00% 0/15	0.00% 0/13	8.3% 1/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
Psychiatric disorders Anxiety	0.00% 0/11	6.7% 1/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Psychiatric disorders Insomnia	0.00% 0/11	0.00% 0/15	7.7% 1/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	0.00% 0/20	0.00% 0/5	6.2% 1/16
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/11	0.00% 0/15	0.00% 0/13	8.3% 1/12	0.00% 0/20	0.00% 0/5	18.8% 3/16
Skin and subcutaneous tissue disorders Dermatitis	9.1% 1/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	6.2% 1/16
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	15.0% 3/20	0.00% 0/5	0.00% 0/16
Skin and subcutaneous tissue disorders Erythema	0.00% 0/11	0.00% 0/15	0.00% 0/13	8.3% 1/12	10.0% 2/20	0.00% 0/5	0.00% 0/16
Skin and subcutaneous tissue disorders Rash	0.00% 0/11	0.00% 0/15	23.1% 3/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	0.00% 0/16
Skin and subcutaneous tissue disorders Skin fissures	0.00% 0/11	0.00% 0/15	0.00% 0/13	8.3% 1/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Skin and subcutaneous tissue disorders Skin irritation	0.00% 0/11	0.00% 0/15	0.00% 0/13	8.3% 1/12	0.00% 0/20	0.00% 0/5	0.00% 0/16
Skin and subcutaneous tissue disorders Umbilical erythema	0.00% 0/11	0.00% 0/15	0.00% 0/13	0.00% 0/12	5.0% 1/20	0.00% 0/5	0.00% 0/16

Additional Information

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Phone: 1-800-718-1021

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER