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

NCT03646721 | Completed Phase 1 FDA Drug

• 1 other identifier: DA1241_DM_Ib
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (8)

• 12-lead ECGs

  Change from baseline in QTcF (msec)

  Throughout study duration, i.e., about 10 weeks (Part1) and about 14-16 weeks (Part2), respectively

• Blood pressure

  Change from baseline in blood pressure (mmHg)

  Throughout study duration, i.e., about 10 weeks (Part1) and about 14-16 weeks (Part2), respectively

• Heart rate

  Change from baseline in heart rate (bpm)

  Throughout study duration, i.e., about 10 weeks (Part1) and about 14-16 weeks (Part2), respectively

• Body temperature

  Change from baseline in oral body temperature (°C)

  Throughout study duration, i.e., about 10 weeks (Part1) and about 14-16 weeks (Part2), respectively

• Respiratory rate

  Change from baseline in respiratory rate (bpm)

  Throughout study duration, i.e., about 10 weeks (Part1) and about 14-16 weeks (Part2), respectively

• Physical examination

  Incidence and severity of clinical findings on physical examination

  Throughout study duration, i.e., about 10 weeks (Part1) and about 14-16 weeks (Part2), respectively

• Clinical laboratory testing

  Incidence and severity of clinical laboratory abnormality

  Throughout study duration, i.e., about 10 weeks (Part1) and about 14-16 weeks (Part2), respectively

• Adverse event

  Incidence and severity of adverse event

  Throughout study duration, i.e., about 10 weeks (Part1) and about 14-16 weeks (Part2), respectively

Secondary Outcomes (21)

• Maximum concentration of DA-1241 (Cmax)

  Through the treatment period; 24 hours

• Time of maximum plasma DA-1241 concentration (Tmax)

  Through the treatment period; 24 hours

• Area under the concentration-time curve (AUC)

  Through the treatment period; 9 days

• Apparent terminal elimination half-life (t½)

  Through the treatment period; 9 days

• Apparent total systemic clearance after oral administration (CL/F)

  Through the treatment period; 9 days

Other Outcomes (1)

• Assessment of key metabolite(s) of DA-1241

  Through the treatment period; 41 days

Study Arms (5)

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

EXPERIMENTAL

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).

Drug: DA-1241

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

PLACEBO COMPARATOR

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).

Drug: Placebo

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

EXPERIMENTAL

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).

Drug: DA-1241

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

PLACEBO COMPARATOR

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).

Drug: Placebo

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

ACTIVE COMPARATOR

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).

Drug: Sitagliptin

Interventions

DA-1241 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] DA-1241 : 6 subjects in each cohort(Cohort 1-3); [Part2] DA-1241 : 15 subjects in each cohort(Cohort 4-6)

Placebo DRUG

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

[Part1] Placebo : 2 subjects in each cohort(Cohort 1-3); [Part2] Placebo : 5 subjects in each cohort(Cohort 4-6)

Sitagliptin DRUG

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

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

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male subjects
• Age ≥ 18 to ≤ 70 years of age.
• Body mass index (BMI) ≥ 18.5 to ≤ 29.9 kg/m2.
• Non-diabetic, fasting plasma glucose (FPG) of \< 100 mg/dL (measured with YSI at site; one repeat test is allowed)
• HbA1c \< 5.7 %
• 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.
• 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.
• Upon review, agree to participate and sign informed consent

You may not qualify if:

• Resting blood pressure (BP) \> 140/90 mmHg or \< 90/60 mmHg. Subjects BP may be re-checked.
• 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.
• History of any serious adverse reaction or hypersensitivity to any of the investigational product components or medicinal products with similar chemical structure.
• 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.
• 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.
• Subject shows evidence of significant active neuropsychiatric disease, including taking prescription medication for such diseases (including anti-depressant /anti-anxiety medication),
• 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)
• Long QT syndrome or family history of long QT syndrome or corrected QT interval (QTcF) \> 450 ms at screening.
• Liver function test results of AST and/or ALT ≥ 1.5 upper limit of normal (ULN).
• Subject had a history of vaso-vagal syncope within 5 years.
• History of any major surgery within 6 months.
• History of any active infection, other than mild viral illness within 30 days prior to dosing.
• 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.
• Subjects with a positive urine nicotine/cotinine dipstick test.
• 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).

Sponsors & Collaborators

• Dong-A ST Co., Ltd.: lead

Study Sites (4)

Clinical Site

Chula Vista, California, 91911, United States

Location

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

Location

High Point Clinical Trials Center

High Point, North Carolina, 27265, United States

Location

Rainier Clinical Research Center

Renton, Washington, 98057, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

DA-1241; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: August 24, 2018
• Study Start: August 29, 2018
• Primary Completion: May 7, 2020
• Study Completion: May 7, 2020
• Last Updated: February 11, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)