A Study to Evaluate the Safety, Tolerability, PK and PD of DA-1241 in Healthy Male Subjects and Subjects With T2DM

NCT ID: NCT03646721

Last Updated: 2021-02-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

108 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-29

Study Completion Date

2020-05-07

Brief Summary

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This is a double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, tolerability, PK and PD of DA-1241 in healthy male subjects and subjects with T2DM

Detailed Description

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Conditions

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Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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[Part1] DA-1241 : 6 subjects in each cohort(Cohort 1-3)

Subjects will participate in 1 of 3 cohorts consisting of 8 subjects per cohort. Within cohorts, subjects will be randomized to a ratio of 6:2 (DA-1241 to matching placebo).

Group Type EXPERIMENTAL

DA-1241

Intervention Type DRUG

\[Part1\] Administration once daily for 28 days; Dose strength for each cohort (Cohort 1, 2 and 3) is planned as 50mg, 100mg and 200mg, respectively.

\[Part2\] Administration once daily for 56 days; Dose strength for each cohort (Cohort 4, 5 and 6) is planned as 25mg, 50mg and 100mg, respectively.

(Dose escalation and dose level decisions for subsequent cohorts will be made via interim dose escalation review meetings.)

[Part1] Placebo : 2 subjects in each cohort(Cohort 1-3)

Subjects will participate in 1 of 3 cohorts consisting of 8 subjects per cohort. Within cohorts, subjects will be randomized to a ratio of 6:2 (DA-1241 to matching placebo).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

\[Part1\] Administration once daily for 28 days. \[Part2\] Administration once daily for 56 days.

[Part2] DA-1241 : 15 subjects in each cohort(Cohort 4-6)

Subjects will participate in 1 of 3 cohorts consisting of 25 subjects per cohort. Within cohorts, subjects will be randomized to a ratio of 3:1:1 (DA-1241 to matching placebo and active comparator).

Group Type EXPERIMENTAL

DA-1241

Intervention Type DRUG

\[Part1\] Administration once daily for 28 days; Dose strength for each cohort (Cohort 1, 2 and 3) is planned as 50mg, 100mg and 200mg, respectively.

\[Part2\] Administration once daily for 56 days; Dose strength for each cohort (Cohort 4, 5 and 6) is planned as 25mg, 50mg and 100mg, respectively.

(Dose escalation and dose level decisions for subsequent cohorts will be made via interim dose escalation review meetings.)

[Part2] Placebo : 5 subjects in each cohort(Cohort 4-6)

Subjects will participate in 1 of 3 cohorts consisting of 25 subjects per cohort. Within cohorts, subjects will be randomized to a ratio of 3:1:1 (DA-1241 to matching placebo and active comparator).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

\[Part1\] Administration once daily for 28 days. \[Part2\] Administration once daily for 56 days.

[Part2] Sitagliptin : 5 subjects in each cohort(Cohort 4-6)

Subjects will participate in 1 of 3 cohorts consisting of 25 subjects per cohort. Within cohorts, subjects will be randomized to a ratio of 3:1:1 (DA-1241 to matching placebo and active comparator).

Group Type ACTIVE_COMPARATOR

Sitagliptin

Intervention Type DRUG

\[Part2\] Administration of Sitagliptin 100mg once daily for 56 days.

Interventions

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DA-1241

\[Part1\] Administration once daily for 28 days; Dose strength for each cohort (Cohort 1, 2 and 3) is planned as 50mg, 100mg and 200mg, respectively.

\[Part2\] Administration once daily for 56 days; Dose strength for each cohort (Cohort 4, 5 and 6) is planned as 25mg, 50mg and 100mg, respectively.

(Dose escalation and dose level decisions for subsequent cohorts will be made via interim dose escalation review meetings.)

Intervention Type DRUG

Placebo

\[Part1\] Administration once daily for 28 days. \[Part2\] Administration once daily for 56 days.

Intervention Type DRUG

Sitagliptin

\[Part2\] Administration of Sitagliptin 100mg once daily for 56 days.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Healthy male subjects
2. Age ≥ 18 to ≤ 70 years of age.
3. Body mass index (BMI) ≥ 18.5 to ≤ 29.9 kg/m2.
4. Non-diabetic, fasting plasma glucose (FPG) of \< 100 mg/dL (measured with YSI at site; one repeat test is allowed)
5. HbA1c \< 5.7 %
6. Non-smoker smoker, defined as: Non-smoker for \>12 months (ie, subject has not smoked or used any tobacco product for the 12 months prior to the start of the study) confirmed by a negative nicotine/cotinine test.
7. Male subjects must be surgically sterile, or engaged with partners of non-childbearing potential, or if engaged with partners of childbearing potential, the subject and his partner must be willing to use contraceptive methods until 3 months after the last day of IP administration. Males must not donate sperms during the study and until 3 months after the last day of IP administration.
8. Upon review, agree to participate and sign informed consent


1. Male and female subjects with T2DM \> 6 months.
2. Age ≥ 18 to ≤ 70 years of age.
3. Body mass index (BMI) ≤ 35 kg/m2.
4. On stable therapy with metformin monotherapy or metformin in combination with other oral antidiabetic drugs (OADs) ≥ 1 month. (OADs except metformin will be washed-out prior to the first dosing)
5. HbA1c ≥ 6.5 to ≤ 10%
6. Female and male subjects must agree to use highly effective methods of birth control until 120 days after the last day of IP administration, or must be surgically sterile or postmenopausal. Males must not donate sperm during the study and until 120 days after the last day of IP administration.
7. Upon review, agree to participate and sign informed consent.

Exclusion Criteria

1. Resting blood pressure (BP) \> 140/90 mmHg or \< 90/60 mmHg. Subjects BP may be re-checked.
2. Participation in an investigational drug/device study within 30 days or 5 half-lives within the last dose of any study drug, whichever is longer.
3. History of any serious adverse reaction or hypersensitivity to any of the investigational product components or medicinal products with similar chemical structure.
4. Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders or abnormalities, or other major systemic disease that, according to the investigator, would unduly risk the subject's safety or may impact the conduct of the study.
5. History of or acute significant gastrointestinal disorder (eg, peptic ulcers, severe GERD), gastric surgery, including surgical treatment for obesity (eg, bariatric surgery, gastric banding), gastric bypass or antrectomy or small bowel resection \>20cm or any disorder that would interfere with the swallowing, absorption, distribution, metabolism and excretion of the investigational product. Surgery for appendicitis is acceptable.
6. Subject shows evidence of significant active neuropsychiatric disease, including taking prescription medication for such diseases (including anti-depressant /anti-anxiety medication),
7. Presence of clinically significant physical, laboratory, or ECG findings at Screening that, in the opinion of the Investigator, may interfere with any aspect of study conduct or interpretation of results, or may present a safety issue to that particular subject. (Laboratory results may be re-checked once on a separate day per Investigator discretion)
8. Long QT syndrome or family history of long QT syndrome or corrected QT interval (QTcF) \> 450 ms at screening.
9. Liver function test results of AST and/or ALT ≥ 1.5 upper limit of normal (ULN).
10. Subject had a history of vaso-vagal syncope within 5 years.
11. History of any major surgery within 6 months.
12. History of any active infection, other than mild viral illness within 30 days prior to dosing.
13. Known history or positive test of hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus type 1 (HIV-1) or 2 (HIV-2) antibody.
14. Subjects with a positive urine nicotine/cotinine dipstick test.
15. History of alcohol abuse as judged by the Investigator within approximately 1 year. Average weekly alcohol intake \> 21 units/week or are unwilling to stop alcohol consumption from 24 hours prior to each dosing until discharged from the clinical research unit (CRU). Positive alcohol test at Screening. (One unit of alcohol equals about 250 mL of beer or lager, 100 mL of wine, or 35 mL of spirits).
16. History of illicit drug abuse, within approximately 1 year or evidence of current use as judged by the Investigator. Positive drug test, including marijuana, at Screening.
17. Donation or loss of \> 500 mL of blood within 56 days.
18. Chronic use of over-the-counter or prescription medication within 7 or 14 days prior to dosing per Investigator's discretion (apart from vitamin/mineral supplements, occasional paracetamol, or birth control methods).
19. Unable to comply with the safety monitoring requirements of this clinical study or is considered by the investigator to be an unsuitable candidate for the study.

\<Part 2\>


1. A subject who has acute proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, especially autonomic neuropathy, as judged by the Investigator.
2. Recurrent major hypoglycemia or hypoglycemic unawareness or recent ketoacidosis, as judged by the Investigator.
3. Persistent blood pressure (BP) systolic or diastolic \> 160/90 mmHg or \< 90/60 mmHg. Subjects BP may be re-checked per site SOP. Treatment with stable doses of antihypertensive medication for 2 months prior to screening are allowed.
4. Pregnant or lactating women.
5. Participation in an investigational drug/device study within 30 days or 5 half-lives within the last dose of any study drug, whichever is longer.
6. History of any serious adverse reaction or hypersensitivity to any of the investigational product components or medicinal products with similar chemical structure.
7. Current use of any prescribed or non-prescribed drugs (other than current treatment for diabetes mellitus or birth control methods) that are known to interfere with glucose or insulin metabolism, including but not limited to oral corticosteroids, GLP-1 receptor agonists, monoamine oxidase (MAO) inhibitors, growth hormone, non-selective β-blockers and lipid lowering medication. Lipid lowering medications will be washed-out prior to the first dosing if subjects take medication for primary prevention.
8. History of administration or current use of thiazolidinediones (TZDs).
9. Chronic use of acetaminophen, as acetaminophen is not allowed during the CGMS periods in the study.
10. Unable to tolerate tape adhesive in the area of sensor placement.
11. Subject has any unresolved adverse skin condition in the area of sensor placement (eg, psoriasis, rash, Staphylococcus infection).
12. History of or acute significant gastrointestinal disorder (eg, peptic ulcers, severe GERD), gastric surgery, gastric bypass or antrectomy or small bowel resection or any disorder that would interfere with the swallowing, absorption, distribution, metabolism and excretion of the investigational product. Surgery for appendicitis is acceptable.
13. History of renal disease or abnormal kidney function tests at Screening (eGFR \< 60 mL/min/1.73m2 as estimated using the MDRD equation).
14. Clinically significant abnormal laboratory test, in particular, elevated liver enzymes (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels \> 2 times the upper limit of normal (ULN)). (Laboratory results may be re-checked once on a separate day per Investigator discretion)
15. Any history of heart disease, defined as symptomatic heart failure (New York Heart Association class III or IV), myocardial infarction, coronary artery bypass graft surgery, or angioplasty, unstable angina requiring medication, transient ischemic attack, cerebral infarct, or cerebral hemorrhage.
16. History of any clinically or active significant gastrointestinal, cardiovascular, hematological, psychiatric, renal, hepatic, pancreatic or neurological abnormality that could interfere with the safety or results of this study as judged by the Investigator.
17. Subject shows evidence of significant active neuropsychiatric disease. Subjects that are stable and controlled by stable doses of selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), antipsychotics and lithium for ≥ 6 months prior to screening are allowed.
18. Presence of clinically significant physical or ECG findings (eg, QTcF \> 450 msec for males, QTcF \> 470 msec for females, left bundle branch block (LBBB)) at Screening that, in the opinion of the Investigator, may interfere with any aspect of study conduct or interpretation of results, or may present a safety issue to that particular subject.
19. History of any major surgery within 6 months.
20. History of any active infection, other than mild viral illness within 30 days prior to the first dosing.
21. Known history or positive test of hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus type 1 (HIV-1) or 2 (HIV-2) antibody.
22. Smoking \> 10 cigarettes per day or equivalent use of any tobacco product (eg, nicotine patch) within 6 months prior to Screening. Subjects must be able to refrain from smoking during each in-house period.
23. History of alcohol abuse as judged by the Investigator within approximately 1 year. Average weekly alcohol intake \> 21 units/week (males) and \> 14 units/week (females) or are unwilling to stop alcohol consumption from 24 hours prior to each check-in for in-house and outpatient visits and throughout the in-house periods until discharged from the clinical research unit (CRU) and are unwilling to limit alcohol consumption during outpatient periods. Positive alcohol test at Screening. (One unit of alcohol equals about 250 mL of beer or lager, 100 mL of wine, or 35 mL of spirits).
24. History of illicit drug abuse, within approximately 1 year or evidence of current use as judged by the Investigator. Positive drug test, including marijuana, at Screening.
25. Donation or loss of \> 500 mL of blood within 56 days.
26. Unable to comply with the safety monitoring requirements of this clinical study or is considered by the investigator to be an unsuitable candidate for the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Dong-A ST Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Clinical Site

Chula Vista, California, United States

Site Status

Clinical Pharmacology of Miami

Miami, Florida, United States

Site Status

High Point Clinical Trials Center

High Point, North Carolina, United States

Site Status

Rainier Clinical Research Center

Renton, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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DA1241_DM_Ib

Identifier Type: -

Identifier Source: org_study_id

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