3283K1-1008-US: Study Evaluating Safety, Tolerability, And Action Of OAP-189 In Subjects With Type 2 Diabetes On Metformin
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00970593
Collaborator
(none)
92
2
2
22.7
46
2
Study Details
Study Description
Brief Summary
This is a study to evaluate the safety, tolerability, and activity of OAP-189 in subjects with type 2 diabetes who are taking metformin for their diabetes.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
92 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A RANDOMIZED, PARALLEL-GROUP, OPEN-LABEL, PLACEBO CONTROLLED STUDY OF THE EFFECT OF OAP-189 ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF METFORMIN IN DIABETIC SUBJECTS.
Actual Study Start Date
:
Sep 2, 2009
Actual Primary Completion Date
:
Jul 25, 2011
Actual Study Completion Date
:
Jul 25, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: OAP-189
|
Drug: OAP-189
Group 1: OAP-189 BID (0.2 mg BID) x 7 days Group 2: OAP-189 (0.4 mg BID) x 7 days Group 3: OAP-189 QD (0.9 mg x 7 days followed by 1.2 mg x 7 days; MR formulation) Group 4: OAP-189 QD (1.2 mg x 7 days followed by 1.6 mg x 7 days; MR formulation) Group 5: OAP-189 QD (1.2 mg x 7 days followed by 1.6 mg x 7 days; different MR formulation) Group 6: OAP-189 QD (1.2 mg x 7 days followed by 1.6 mg x 7 days; different MR formulation)
|
| Placebo Comparator: 2
|
Drug: placebo comparator
Group 1 & 2: PBO x 7 days BID Group 3: PBO QD x 14 days Group 4: PBO QD x 14 days Group 5: PBO QD x 14 days Group 6: PBO QD x 14 days
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Clinically Significant Physical Examination Abnormalities [Baseline up to 17 days after last dose of study drug (Day 31)]
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.
- Number of Participants With Clinically Significant Vital Signs Abnormalities [Baseline up to 17 days after last dose of study drug (Day 31)]
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.
- Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities [Baseline up to 17 days after last dose of study drug (Day 31)]
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).
- Number of Participants With Clinically Significant Laboratory Abnormalities [Baseline up to 17 days after last dose of study drug (Day 31)]
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.
- Number of Participants With Injection Site Reactions [Baseline up to 17 days after last dose of study drug (Day 31)]
Injection site reactions included irritation, erythema, pain, hematoma, inflammation.
- Number of Participants With Clinically Significant Fasting Glucose Level Abnormalities [Baseline up to 17 days after last dose of study drug (Day 31)]
Criteria: Blood glucose levels >15 milligram per deciliter (mg/dL) above ULN or >15 mg/dL below LLN.
- Number of Participants With Hypoglycaemia [Baseline up to 17 days after last dose of study drug (Day 31)]
Hypoglycaemia is a condition characterized by abnormally low blood glucose (blood sugar) levels, usually <=50 mg/dL.
- Number of Participants With Drug-Induced Liver Injury [Baseline up to 17 days after last dose of study drug (Day 31)]
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.
- Change From Baseline in Predose Fasting Glucose Levels at Day 8 [Baseline, Day 8]
Fasting glucose levels were determined before administration of OAP-189 using a glucometer.
- Change From Baseline in Predose Fasting Glucose Levels at Day 15 [Baseline, Day 15]
Fasting glucose levels were determined before administration of OAP-189 using a glucometer.
Other Outcome Measures
- Plasma Concentration Versus Time Summary of Metformin Following Single Dose of OAP-189 [Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6 hours post-dose on Day 14]
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.
- Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 [Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 hours post-dose on Day 7]
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.
- Plasma Concentration Versus Time Summary of Single Dose of OAP-189 [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]
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.
- Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 [Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 hours post-dose on Day 7]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Subjects must have been diagnosed with type 2 diabetes, with HbA1c level >=7.0% and <=11.0% and a fasting glucose level <=280 mg/dL.
-
Men or women of nonchildbearing potential (WONCBP), aged 18 to 65 years inclusive on study day 1.
-
Body mass index in the range of 27 to 40kg/m² (inclusive) and body weight >=50 kg.
-
Subjects must be otherwise generally healthy, but may be enrolled with a stable chronic illness, if it is well controlled and does not interfere with the primary objective of the study.
-
Subjects must currently be treated for diabetes with metformin alone at a total daily dose of >=1gm (administered QD or BID) and that dose must have been stable for at least 4 weeks before study day 1.
-
Nonsmoker.
Exclusion Criteria:
-
Any significant disease with the exception of diabetes mellitus.
-
Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the investigational product.
-
Acute disease state (eg, nausea, vomiting, fever, or diarrhea) within 7 days before study day 1.
-
Any clinically important problems in physical examination results, vitals sign measurements, ECGs, or clinical laboratory test results.
-
Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies.
-
Positive findings of urine drug screen
-
Use of any investigational or non-permitted prescription drug within 30 days before investigational product administration.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Profil Institute for Clincal Research | Chula Vista | California | United States | 91911 |
| 2 | Cetero Research - Miami | Miami Gardens | Florida | United States | 33169 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00970593
Other Study ID Numbers:
- 3283K1-1008
- B2201004
First Posted:
Sep 2, 2009
Last Update Posted:
Nov 2, 2020
Last Verified:
Oct 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Period Title: Overall Study | |||||||
| STARTED | 11 | 15 | 13 | 12 | 20 | 5 | 16 |
| COMPLETED | 10 | 14 | 7 | 12 | 20 | 5 | 14 |
| NOT COMPLETED | 1 | 1 | 6 | 0 | 0 | 0 | 2 |
Baseline Characteristics
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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 of all reporting groups |
| Overall Participants | 11 | 15 | 13 | 12 | 20 | 5 | 16 | 92 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||
| Mean (Standard Deviation) [years] |
55.00
(8.65)
|
53.60
(6.33)
|
52.69
(3.12)
|
54.92
(6.69)
|
51.50
(9.64)
|
53.80
(9.34)
|
54.75
(6.83)
|
53.57
(7.33)
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
3
27.3%
|
4
26.7%
|
3
23.1%
|
4
33.3%
|
4
20%
|
2
40%
|
6
37.5%
|
26
28.3%
|
| Male |
8
72.7%
|
11
73.3%
|
10
76.9%
|
8
66.7%
|
16
80%
|
3
60%
|
10
62.5%
|
66
71.7%
|
Outcome Measures
| Title | Number of Participants With Clinically Significant Physical Examination Abnormalities |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to 17 days after last dose of study drug (Day 31) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomly assigned participants who received at least 1 dose of study medication. |
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 11 | 15 | 13 | 12 | 20 | 5 | 16 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Clinically Significant Vital Signs Abnormalities |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to 17 days after last dose of study drug (Day 31) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomly assigned participants who received at least 1 dose of study medication. |
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 11 | 15 | 13 | 12 | 20 | 5 | 16 |
| Number [participants] |
1
9.1%
|
2
13.3%
|
1
7.7%
|
2
16.7%
|
4
20%
|
0
0%
|
1
6.3%
|
| Title | Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities |
|---|---|
| Description | 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). |
| Time Frame | Baseline up to 17 days after last dose of study drug (Day 31) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 11 | 15 | 8 | 12 | 20 | 5 | 14 |
| Number [participants] |
0
0%
|
0
0%
|
2
15.4%
|
4
33.3%
|
4
20%
|
0
0%
|
7
43.8%
|
| Title | Number of Participants With Clinically Significant Laboratory Abnormalities |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to 17 days after last dose of study drug (Day 31) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomly assigned participants who received at least 1 dose of study medication. |
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 11 | 15 | 13 | 12 | 20 | 5 | 16 |
| Number [participants] |
10
90.9%
|
15
100%
|
13
100%
|
9
75%
|
19
95%
|
5
100%
|
15
93.8%
|
| Title | Number of Participants With Injection Site Reactions |
|---|---|
| Description | Injection site reactions included irritation, erythema, pain, hematoma, inflammation. |
| Time Frame | Baseline up to 17 days after last dose of study drug (Day 31) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomly assigned participants who received at least 1 dose of study medication. |
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 11 | 15 | 13 | 12 | 20 | 5 | 16 |
| Irritation |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5%
|
0
0%
|
1
6.3%
|
| Erythema |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5%
|
0
0%
|
1
6.3%
|
| Pain |
0
0%
|
0
0%
|
0
0%
|
2
16.7%
|
1
5%
|
0
0%
|
0
0%
|
| Hematoma |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
15%
|
0
0%
|
1
6.3%
|
| Inflammation |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
6.3%
|
| Title | Number of Participants With Clinically Significant Fasting Glucose Level Abnormalities |
|---|---|
| Description | Criteria: Blood glucose levels >15 milligram per deciliter (mg/dL) above ULN or >15 mg/dL below LLN. |
| Time Frame | Baseline up to 17 days after last dose of study drug (Day 31) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomly assigned participants who received at least 1 dose of study medication. |
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 11 | 15 | 13 | 12 | 20 | 5 | 16 |
| Number [participants] |
10
90.9%
|
15
100%
|
13
100%
|
9
75%
|
19
95%
|
5
100%
|
15
93.8%
|
| Title | Number of Participants With Hypoglycaemia |
|---|---|
| Description | Hypoglycaemia is a condition characterized by abnormally low blood glucose (blood sugar) levels, usually <=50 mg/dL. |
| Time Frame | Baseline up to 17 days after last dose of study drug (Day 31) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomly assigned participants who received at least 1 dose of study medication. |
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 11 | 15 | 13 | 12 | 20 | 5 | 16 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
2
16.7%
|
1
5%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Drug-Induced Liver Injury |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to 17 days after last dose of study drug (Day 31) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomly assigned participants who received at least 1 dose of study medication. |
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). |
| Measure Participants | 11 | 15 | 13 | 12 | 20 | 5 | 16 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Change From Baseline in Predose Fasting Glucose Levels at Day 8 |
|---|---|
| Description | Fasting glucose levels were determined before administration of OAP-189 using a glucometer. |
| Time Frame | Baseline, Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | 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 | Placebo MR |
|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). |
| Measure Participants | 13 | 12 | 20 | 16 |
| Baseline |
10.02
(2.373)
|
10.06
(2.583)
|
9.27
(2.148)
|
9.01
(1.769)
|
| Change at Day 8 |
-1.37
(2.222)
|
-2.75
(1.663)
|
-2.47
(1.400)
|
-0.25
(1.166)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | OAP-189 0.2 mg IR, OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg |
|---|---|---|
| Comments | The Mixed model used fixed effects of treatment, study day and treatment by study day interaction. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.75 | |
| Confidence Interval |
(2-Sided) 95% -1.79 to 0.29 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.526 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | OAP-189 0.4 mg IR, OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg |
|---|---|---|
| Comments | The Mixed model used fixed effects of treatment, study day and treatment by study day interaction. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.90 | |
| Confidence Interval |
(2-Sided) 95% -2.98 to -0.83 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.543 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 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 |
|---|---|---|
| Comments | The Mixed model used fixed effects of treatment, study day and treatment by study day interaction. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -2.15 | |
| Confidence Interval |
(2-Sided) 95% -3.06 to -1.24 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.458 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Predose Fasting Glucose Levels at Day 15 |
|---|---|
| Description | Fasting glucose levels were determined before administration of OAP-189 using a glucometer. |
| Time Frame | Baseline, Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | 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 | Placebo MR |
|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). | 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). |
| Measure Participants | 7 | 12 | 20 | 14 |
| Mean (Standard Deviation) [millimole per liter] |
-2.62
(0.998)
|
-3.87
(1.783)
|
-3.49
(1.643)
|
-0.33
(1.273)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | OAP-189 0.2 mg IR, OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg |
|---|---|---|
| Comments | The Mixed model used fixed effects of treatment, study day and treatment by study day interaction. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | -2.37 | |
| Confidence Interval |
(2-Sided) 95% -3.52 to -1.22 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.580 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | OAP-189 0.4 mg IR, OAP-189 MR (0.1:1 Z/P Ratio) 1.2 mg Followed by 1.6 mg |
|---|---|---|
| Comments | The Mixed model used fixed effects of treatment, study day and treatment by study day interaction. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -3.18 | |
| Confidence Interval |
(2-Sided) 95% -4.16 to -2.20 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.495 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 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 |
|---|---|---|
| Comments | The Mixed model used fixed effects of treatment, study day and treatment by study day interaction. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -3.14 | |
| Confidence Interval |
(2-Sided) 95% -4.01 to -2.28 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.437 |
|
| Estimation Comments | ||
| Title | Plasma Concentration Versus Time Summary of Metformin Following Single Dose of OAP-189 |
|---|---|
| Description | 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. |
| Time Frame | Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6 hours post-dose on Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | 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 |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 7 | 12 |
| Pre-dose |
318.7
(140.36)
|
455.6
(246.43)
|
| 1 hour post dose |
899.1
(344.02)
|
990.9
(453.01)
|
| 2 hour post dose |
885.4
(364.20)
|
1112
(652.61)
|
| 3 hour post dose |
881.4
(357.83)
|
1063
(613.86)
|
| 4 hour post dose |
912.3
(381.22)
|
943.7
(474.35)
|
| 6 hour post dose |
869.7
(215.27)
|
804.8
(349.20)
|
| Title | Plasma Concentration Versus Time Summary of Metformin Following Multiple Dose of OAP-189 |
|---|---|
| Description | 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. |
| Time Frame | Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg IR |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 10 | 14 |
| Pre-dose |
544.7
(334.72)
|
558.9
(386.19)
|
| 1 hour post dose |
998.8
(360.42)
|
1276
(858.80)
|
| 2 hour post dose |
980.7
(336.37)
|
1084
(582.26)
|
| 3 hour post dose |
995.8
(342.21)
|
985.5
(424.50)
|
| 4 hour post dose |
938.3
(355.38)
|
974.7
(504.81)
|
| 6 hour post dose |
804.6
(343.23)
|
854.0
(415.21)
|
| 8 hour post dose |
617.0
(265.18)
|
735.4
(350.03)
|
| 10 hour post dose |
462.4
(194.50)
|
658.1
(457.83)
|
| 12 hour post dose |
987.2
(442.22)
|
1029
(477.30)
|
| 14 hour post dose |
972.6
(415.05)
|
976.4
(497.10)
|
| 16 hour post dose |
889.7
(465.26)
|
906.1
(418.88)
|
| 24 hour post dose |
455.1
(488.53)
|
503.5
(334.27)
|
| Title | Plasma Concentration Versus Time Summary of Single Dose of OAP-189 |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | 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 |
|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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). |
| Measure Participants | 13 | 12 | 20 |
| Day 7: Pre-dose |
2.173
(0.55480)
|
3.253
(1.2371)
|
2.313
(1.0927)
|
| Day 7: 2 hour post dose |
8.065
(2.8023)
|
11.56
(8.9549)
|
5.380
(3.2235)
|
| Day 7: 4 hour post dose |
10.40
(4.8907)
|
14.21
(10.429)
|
6.113
(2.8196)
|
| Day 7: 6 hour post dose |
9.173
(4.4176)
|
11.71
(6.7732)
|
5.249
(2.7225)
|
| Day 14: Pre-dose |
3.350
(0.85499)
|
4.550
(2.0888)
|
3.404
(1.6691)
|
| Day 14: 1 hour post dose |
6.740
(3.4367)
|
18.46
(34.903)
|
7.686
(5.0265)
|
| Day 14: 2 hour post dose |
9.747
(4.8634)
|
19.53
(23.410)
|
8.492
(4.0211)
|
| Day 14: 3 hour post dose |
11.23
(4.4618)
|
19.79
(17.035)
|
8.969
(3.6809)
|
| Day 14: 4 hour post dose |
11.70
(4.4452)
|
17.88
(12.785)
|
8.911
(3.5977)
|
| Day 14: 6 hour post dose |
9.611
(3.7471)
|
14.97
(10.234)
|
7.353
(3.2211)
|
| Day 14: 8 hour post dose |
8.094
(3.3158)
|
12.83
(7.6125)
|
6.326
(2.7418)
|
| Day 14: 10 hour post dose ( |
6.991
(2.6902)
|
10.13
(5.8597)
|
5.845
(2.1174)
|
| Day 14: 12 hour post dose |
5.431
(2.0067)
|
7.939
(4.6575)
|
5.152
(2.3713)
|
| Day 14: 14 hour post dose |
4.341
(1.5433)
|
6.708
(3.4394)
|
4.604
(1.7001)
|
| Day 14: 16 hour post dose |
4.160
(0.93113)
|
5.993
(3.0649)
|
4.612
(1.8386)
|
| Day 14: 24 hour post dose |
2.910
(0.70512)
|
3.911
(1.7983)
|
3.688
(1.2721)
|
| Day 14: 48 hour post dose |
1.285
(0.29853)
|
1.781
(1.1929)
|
1.968
(1.1127)
|
| Day 14: 72 hour post dose |
0.4900
(0.43025)
|
1.070
(1.5187)
|
0.8378
(0.72049)
|
| Title | Plasma Concentration Versus Time Summary of Multiple Dose of OAP-189 |
|---|---|
| Description | 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. |
| Time Frame | Pre-dose (2 hours before dosing), 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg IR |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 10 | 14 |
| Pre-dose |
1.667
(1.4404)
|
3.548
(1.9612)
|
| 1 hour post dose |
2.727
(1.4936)
|
4.920
(1.7474)
|
| 2 hour post dose |
4.454
(2.9789)
|
7.824
(2.9187)
|
| 3 hour post dose |
5.614
(3.0258)
|
10.09
(3.9267)
|
| 4 hour post dose |
6.080
(3.0045)
|
11.79
(5.0857)
|
| 6 hour post dose |
5.206
(2.0969)
|
9.204
(4.3138)
|
| 8 hour post dose |
4.064
(1.6576)
|
6.889
(2.7902)
|
| 10 hour post dose |
2.743
(1.0067)
|
5.076
(2.0844)
|
| 12 hour post dose |
5.315
(2.0278)
|
9.376
(3.7875)
|
| 14 hour post dose |
6.976
(2.7327)
|
11.61
(6.2016)
|
| 16 hour post dose |
6.157
(1.8865)
|
10.87
(4.9706)
|
| 24 hour post dose |
1.315
(0.87065)
|
2.591
(1.3243)
|
Adverse Events
| Time Frame | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||
| Arm/Group Title | OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR | |||||||
| Arm/Group Description | 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). | 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). | 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). | 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). | 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). | 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). | 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). | |||||||
All Cause Mortality |
||||||||||||||
| OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||
Serious Adverse Events |
||||||||||||||
| OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||
| OAP-189 0.2 mg IR | OAP-189 0.4 mg 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 | Placebo IR | Placebo MR | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/11 (54.5%) | 11/15 (73.3%) | 13/13 (100%) | 10/12 (83.3%) | 16/20 (80%) | 1/5 (20%) | 11/16 (68.8%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Ear and labyrinth disorders | ||||||||||||||
| Ear pain | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Tinnitus | 0/11 (0%) | 0/15 (0%) | 2/13 (15.4%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Eye disorders | ||||||||||||||
| Vision blurred | 0/11 (0%) | 1/15 (6.7%) | 0/13 (0%) | 1/12 (8.3%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Abdominal discomfort | 0/11 (0%) | 0/15 (0%) | 2/13 (15.4%) | 3/12 (25%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Abdominal distension | 0/11 (0%) | 2/15 (13.3%) | 4/13 (30.8%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Abdominal pain | 0/11 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Abdominal pain upper | 1/11 (9.1%) | 1/15 (6.7%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Constipation | 0/11 (0%) | 2/15 (13.3%) | 3/13 (23.1%) | 3/12 (25%) | 0/20 (0%) | 0/5 (0%) | 2/16 (12.5%) | |||||||
| Diarrhoea | 1/11 (9.1%) | 2/15 (13.3%) | 3/13 (23.1%) | 2/12 (16.7%) | 2/20 (10%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Dry mouth | 0/11 (0%) | 1/15 (6.7%) | 2/13 (15.4%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Dyspepsia | 0/11 (0%) | 1/15 (6.7%) | 5/13 (38.5%) | 0/12 (0%) | 2/20 (10%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Eructation | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Flatulence | 0/11 (0%) | 2/15 (13.3%) | 3/13 (23.1%) | 2/12 (16.7%) | 0/20 (0%) | 0/5 (0%) | 2/16 (12.5%) | |||||||
| Hyperchlorhydria | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 1/12 (8.3%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Lip dry | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Nausea | 3/11 (27.3%) | 8/15 (53.3%) | 9/13 (69.2%) | 6/12 (50%) | 8/20 (40%) | 0/5 (0%) | 2/16 (12.5%) | |||||||
| Vomiting | 1/11 (9.1%) | 8/15 (53.3%) | 2/13 (15.4%) | 5/12 (41.7%) | 4/20 (20%) | 0/5 (0%) | 2/16 (12.5%) | |||||||
| Vomiting projectile | 0/11 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| General disorders | ||||||||||||||
| Application site irritation | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Asthenia | 1/11 (9.1%) | 2/15 (13.3%) | 0/13 (0%) | 2/12 (16.7%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Chills | 0/11 (0%) | 1/15 (6.7%) | 1/13 (7.7%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Fatigue | 0/11 (0%) | 0/15 (0%) | 1/13 (7.7%) | 1/12 (8.3%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Inflammation | 1/11 (9.1%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Infusion site inflammation | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Injection site erythema | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Injection site haematoma | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 3/20 (15%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Injection site pain | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 2/12 (16.7%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Injection site reaction | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 2/20 (10%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Non-cardiac chest pain | 0/11 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Pain | 1/11 (9.1%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Sluggishness | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Otitis externa | 0/11 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Contusion | 0/11 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Decreased appetite | 0/11 (0%) | 3/15 (20%) | 3/13 (23.1%) | 4/12 (33.3%) | 2/20 (10%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Hypoglycaemia | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 2/12 (16.7%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Polydipsia | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Back pain | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 1/5 (20%) | 0/16 (0%) | |||||||
| Muscle spasms | 0/11 (0%) | 0/15 (0%) | 2/13 (15.4%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Neck pain | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Pain in extremity | 0/11 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Dizziness | 1/11 (9.1%) | 5/15 (33.3%) | 2/13 (15.4%) | 2/12 (16.7%) | 2/20 (10%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Dysgeusia | 0/11 (0%) | 0/15 (0%) | 1/13 (7.7%) | 1/12 (8.3%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Headache | 0/11 (0%) | 3/15 (20%) | 2/13 (15.4%) | 5/12 (41.7%) | 4/20 (20%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Lethargy | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Somnolence | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 1/12 (8.3%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Tremor | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 1/12 (8.3%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Anxiety | 0/11 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Insomnia | 0/11 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Nasal congestion | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 0/20 (0%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Oropharyngeal pain | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 1/12 (8.3%) | 0/20 (0%) | 0/5 (0%) | 3/16 (18.8%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Dermatitis | 1/11 (9.1%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 1/16 (6.3%) | |||||||
| Ecchymosis | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 3/20 (15%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Erythema | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 1/12 (8.3%) | 2/20 (10%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Rash | 0/11 (0%) | 0/15 (0%) | 3/13 (23.1%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Skin fissures | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 1/12 (8.3%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Skin irritation | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 1/12 (8.3%) | 0/20 (0%) | 0/5 (0%) | 0/16 (0%) | |||||||
| Umbilical erythema | 0/11 (0%) | 0/15 (0%) | 0/13 (0%) | 0/12 (0%) | 1/20 (5%) | 0/5 (0%) | 0/16 (0%) | |||||||
Limitations/Caveats
Data for fasting Insulin level abnormalities and capillary glucose level abnormalities was not reported due to change in planned analysis.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00970593
Other Study ID Numbers:
- 3283K1-1008
- B2201004
First Posted:
Sep 2, 2009
Last Update Posted:
Nov 2, 2020
Last Verified:
Oct 1, 2020