A First in Human Study to Assess the Safety, Tolerability of LB54640 in in Healthy Overweight and Obese Subjects

Study Overview
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Brief Summary
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The aim of this 4-weeks randomized double-blind placebo-controlled single and multiple ascending dose study is to assess the Safety and Tolerability of LB54640 in Healthy overweight and obese subjects

Detailed Description
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The study was conducted in 2 parts: Part 1 (Single Ascending Dose) This study part included 6 sequential dose cohorts (S1-S6), enrolling 8 healthy subjects per cohort. Cohort S3 was evaluate the effect of food. Part 2 (Multiple Ascending Dose) This part included 7 sequential dose cohorts (M1-M7), enrolling 8 subjects per cohort. Cohorts was evaluate safety, Pharmacokinetics and Pharmacodynamics parameters in healthy overweight and obese subjects. They were dosed once daily for 28 days with LB54640 or placebo.

Official Title
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Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Assess the Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of Compound LB54640 in Healthy Overweight and Obese Subjects

Conditions
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Obese, Overweight, Healthy

Intervention / Treatment
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* Drug: LB64640
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥ 18 to ≤ 70 years. Body mass index (BMI) ≥ 27 kg/m2, with stable body weight by history for 3 months (defined as change < 5%) HbA1c < 6.5%. Female subjects must be non-pregnant and non-lactating. Females of childbearing potential must use at least two of the medically accepted contraceptive methods, table at least 4 weeks prior to the screening. Ability to provide written informed consent. Exclusion Criteria: History or current diagnosis with T1DM or T2DM. History or current diagnosis of any malignancy. History of pheochromocytoma or insulinoma. History or current diagnosis of cardiac dysrhythmias or heart disease History of surgical treatment for obesity or any other gastrointestinal surgery History of major depression, anxiety, suicidal behavior or attempts, or other psychiatric disorder. Use of approved weight-lowering pharmacotherapy Has a clinically significant history of suicidal ideation or suicidal behavior as assessed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This was a randomized, double-blind, placebo-controlled study conducted in two parts. Study Part 1 had a SAD design to investigate the safety, tolerability, and PK of LB54640 administered orally in healthy overweight and obese subjects. Study Part 1 included a cohort (Cohort S3) to assess the effect of food on LB54640, which was conducted with a blinded, placebo-controlled, two-way crossover design. Study Part 2 had a MAD design to investigate the safety, tolerability, PK, and PD of LB54640 administered orally in healthy overweight and obese subjects
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LB54640<br>5 mg, 25 mg and 200 mg strengths Subjects will be administered once daily and duration vary per each cohorts. Single Ascending Dose (SAD) cohorts : 1 day SAD 1 10mg SAD 2 25mg SAD 3 50mg (Food effect cohort) SAD 4 100mg SAD 5 200mg SAD 6 400mg healthy Multiple Ascending Dose (MAD) cohorts: 28days MAD 1 10mg MAD 2 25mg MAD 3 50mg MAD 4 100mg MAD 5 200mg MAD 6 400mg MAD 7 600mg | Drug: LB64640<br>* The investigational product (IP) LB54640 is provided 5 mg, 25 mg and 200 mg strengths.<br>|
| Placebo Comparator: Placebo<br>matching placebo | Drug: Placebo<br>* Placebo is provided as a matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs) | Number of subjects who experienced adverse events and severity of adverse events | Through study completion upto 6weeks depending on cohorts | 
| Incidence and severity of adverse events of special interest (AESIs) in Part 2 (MAD) | Number of subjects who experienced adverse events of special interest (AESIs) | Through study completion upto 6weeks depending on cohorts | 
| Change from baseline in vital signs (blood pressure) | Absolute values and changes from baseline (BP assessed by 24-hour ambulatory blood pressure monitoring (ABPM);systolic pressure and diastolic pressure will be assessed | Through study completion upto 6weeks depending on cohorts | 
| Change from baseline in vital signs (heart rate) | Absolute values and changes from baseline (HR assessed by 24-hour ambulatory electrocardiography monitoring (12-lead cardiac telemetry; central reader)) | Through study completion upto 6weeks depending on cohorts | 
| Change from baseline in vital signs (weight in kilograms, height in meters) | weight and height will be combined to report BMI in kg/m^2 | Through study completion upto 6weeks depending on cohorts | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics profiles in Plasma for single ascending dose cohort | Peak Plasma Concentration (Cmax) during the dosing periods | Through study completion upto 1week | 
| Pharmacokinetics profiles in Plasma for single ascending dose cohort | Area under the plasma concentration versus time curve (AUC) | Upto 1week | 
| Pharmacokinetics profiles in Plasma for single ascending dose cohort | Terminal half-life (t1/2) | Through study completion upto 1week during the single ascending dose cohort | 
| Pharmacokinetics profiles in urine for single ascending dose cohort | Renal clearance (CLR) | upto 1week | 
| Pharmacokinetics profiles in urine for single ascending dose cohort | Amount of unchanged drug excreted into urine (Ae) for specific collection intervals | Through study completion upto 1week depending on cohorts | 
| Pharmacokinetics profiles in plasma for multiple ascending dose cohort | Maximum concentration (Cmax) | upto 2weeks | 
| Pharmacokinetics profiles in plasma for multiple ascending dose cohort | Area under the concentration-time curve (AUC) during the dosing periods | Through study completion upto 2weeks |