Multiple Ascending Dose Trial of BYK324677 in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
This monocenter trial is conducted to obtain first data on safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) after multiple ascending doses of BYK324677 in humans. In addition, the trial should provide preliminary information on a possible influence of sex, food intake, and posology (once or twice daily administration of BYK324677) to support the further planning of the drug development programme.

Official Title
-----------------
Investigation of Safety/Tolerability, Pharmacokinetics and Pharmacodynamics After Multiple Ascending Doses of BYK324677 in Healthy Volunteers. A Monocentre, Placebo-controlled, Cross-over, Double-blind, Randomised Trial

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: BYK324677


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Given written informed consent Healthy male and female subjects. Assessed as healthy based on a screening examination including medical history, physical examination, blood pressure (systolic ≤140 mmHg, diastolic ≤90 mmHg), pulse rate (within 45-95 bpm), ECG assessment, and clinical laboratory results Body mass index (BMI) between ≥18 and ≤28 kg/m², and a body weight ≥60 kg Exclusion Criteria: History or current evidence of specified diseases History of malignancy in the past 5 years Gain or loss in body weight of more than 5% within the last 2 months or use of weight-loss medication within the last 3 months ECG abnormalities of clinical relevance Suspected hypersensitivity to the trial medication Positive virology tests indicating acute or chronic infections Clinically relevant laboratory parameters outside a specified range Use of specified medications within certain time frames or use of certain co-medications Abuse of alcohol or drugs Dietary habits that would prevent from taking standardised meals Female subjects: positive pregnancy test; lack of medically reliable methods of contraception during the trial Donation of blood Smoking within the last 3 months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BYK324677<br>Dose group I: total daily dose 2 mg (1 mg BID or 2 mg SID) Dose group II: total daily dose 4 mg (2 mg BID or 4 mg SID) Dose group III: total daily dose 6 mg (3 mg BID or 6 mg SID) In each dose group 12 subjects (8 subjects BYK324677, 4 subjects placebo) are planned. Within each dose group, the subjects will be randomised to either BYK324677 or placebo at a ratio of 2:1. Within each verum group, the subjects will be randomised to one of the 2 treatment sequences (BID/SID or SID/BID, ratio 1:1) and treated in a cross-over manner. | Drug: BYK324677<br>* capsules, administered orally<br>|
| Placebo Comparator: Placebo<br> | Drug: BYK324677<br>* capsules, administered orally<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the safety/tolerability of multiple dosing of BYK324677 given once daily (SID) or twice daily (BID) in healthy volunteers. | Safety/tolerability variables: adverse events (AEs), vital signs (BP, pulse rate, body temperature), 12-lead ECG (PQ [=PR], QRS, QT, QTcF and QTcB intervals, heart rate), laboratory parameters including urinalysis. | during screening, clinical part (treatment) and end-of-trial examination (up to 8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exploratory assessment of the pharmacokinetics (PK) of multiple dosing of BYK324677 (SID or BID) under steady state conditions in healthy volunteers. | Pharmacokinetic variables (e.g. AUC, Cmax, tmax, t1/2) of BYK324677 on Day 1 and Day 5 (single dose i.e. after first Investigational medicinal product (IMP) dose vs steady state) as well as on Day 4 and Day 5 (fed vs fasted, respectively). | during Treatment Period 1 and Period 2 (up to 3 weeks) | 
| Exploratory assessment of the pharmacodynamics (PD) of multiple dosing of BYK324677 (SID or BID) under steady state conditions in healthy volunteers. | Pharmacodynamic variables glucose, insulin, glucagon-like peptide 1 and glucagon on Day -1, Day 4 (fed) and Day 5 (fasted). | during Treatment Period 1 and Period 2 (up to 3 weeks) |