A Single Ascending Dose Study of BTZ043

Study Overview
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Brief Summary
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This study is a randomized, double-blind, placebo-controlled, single ascending dose study to evaluate safety, tolerability, and pharmacokinetics of single doses of BTZ043 in healthy adult volunteers. The study is conducted at a study centre in Germany. Up to 50 male and female participants will be included in this study in up to 5 cohorts; each cohort will consist of 10 subjects: in each cohort 8 subjects will be assigned to BTZ-043 and 2 to placebo. The doses tested will be: 125mg, 250mg, 500mg, 1000mg and 2000mg. Safety will be assessed via regular vital sign measurement, 12-lead ECG parameters, physical examination and safety laboratory assessments. Subjects will be hospitalized from Day -1 until discharge in the morning of Day 3. After completion of all Day 3 assessments of a cohort, blinded safety data will be reviewed and the next dose increment will be decided by the Trial Steering Committee (TSC).

Official Title
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A Randomized, Double Blind, Placebo-controlled, Single Ascending Dose Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Doses of BTZ043 in Healthy Adult Volunteers

Conditions
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Tuberculosis, Tuberculosis, Pulmonary, Bacterial Infections, Lung Diseases, Mycobacterium Infections

Intervention / Treatment
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* Drug: BTZ-043
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent Healthy male or female subjects aged between ≥18 and ≤55 years at screening who are able to read, write, and fully understand the German language BMI between ≥18 and ≤30 kg/m2, with a body weight between ≥55 and ≤90 kg at screening Vital signs within range: pulse rate 50-90 bpm, systolic blood pressure 90-140 mmHg, diastolic blood pressure 50-90 mmHg No clinically significant findings in laboratory tests Women must be of non-childbearing potential, that is, either postmenopausal or premenopausal with documented tubal ligation or hysterectomy or women who are at least 6 weeks post-surgical bilateral oophorectomy Male subjects must agree to use a condom with spermicide when engaging in sexual intercourse during the study period and for 2 months after study drug dosing, if they have not had a vasectomy at least 6 months before study start Male subjects must not donate sperm during the study and for 2 months after study drug dosing Able to swallow the amount of drug in succession Agree not to donate blood (or bloodcomponents) until 1 month after receiving study drug Normal consumption of alcohol Willing to forgo sunbathing and prolonged exposure to sunlight during the study period Willing to forgo strenuous exercise from 72 hours prior to admission until discharge Exclusion Criteria: Any known chronic systemic viral infection Any relevant systemic infection or other systemic illness Vaccination 30 days prior to drug administration Known hypersensitivity to any of the excipients of the study drug A clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders, or have a clinically relevant surgical history or any other medical condition History of or current alcohol or illicit drug abuse Positive results in the urine drug screen or blood alcohol test at admission Current or recent (within the past 3 months before drug administration) use of tobacco or other nicotine-containing product or positive results of cotinine test at screening or admission Use of any prescription or over-the-counter (OTC) drug or herbal product within 14 days before drug administration with exception for sporadic use of ibuprofen or paracetamol for example in case of pain Use of any known drug metabolism enzyme-altering drug or supplement within 14 days before dosing or consumption of foods or beverages containing grapefruit within 48 hours before admission ECG findings in the screening ECG of QTcF-interval over 450 ms; atrioventricular (AV) block with PR-interval over 200 ms, prolongation of the QRS complex over 120 ms, or other changes in the ECG that are clinically relevant as per discretion of the investigator Long QT syndrome, or family history of long QT syndrome or sudden death of unknown or cardiac-related cause Use or planned necessary use of any QT-prolonging agents Participation in another investigational drug study within the previous 30 days before drug administration Any donation of blood, plasma, or platelets or significant loss of blood within the previous 30 days before drug administration Previous randomization in this study Volunteer unwilling or unable to comply with protocol requirements in the judgment of the investigator Vulnerable subject (e.g. person is kept in detention) Employees of the sponsor or subjects who are employees or relatives of the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 125 mg BTZ-043 fasting<br>N=8, 125 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose | Drug: BTZ-043<br>* Powder and solvent for oral suspension<br>|
| Placebo Comparator: Cohort 1: Placebo<br>N=2, matching placebo, powder and solvent for oral solution, single dose | Drug: Placebo<br>* Matching placebo: powder and solvent for oral suspension<br>|
| Experimental: Cohort 2: 250 mg BTZ-043 fasting<br>N=8, 250 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose | Drug: BTZ-043<br>* Powder and solvent for oral suspension<br>|
| Placebo Comparator: Cohort 2: Placebo<br>N=2, matching placebo, powder and solvent for oral solution, single dose | Drug: Placebo<br>* Matching placebo: powder and solvent for oral suspension<br>|
| Experimental: Cohort 3: 500 mg BTZ-043 fasting<br>N=8, 500 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose | Drug: BTZ-043<br>* Powder and solvent for oral suspension<br>|
| Placebo Comparator: Cohort 3: Placebo<br>N=2, matching placebo, powder and solvent for oral solution, single dose | Drug: Placebo<br>* Matching placebo: powder and solvent for oral suspension<br>|
| Experimental: Cohort 4: 1000 mg BTZ-043 fasting<br>N=8, 1000 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose | Drug: BTZ-043<br>* Powder and solvent for oral suspension<br>|
| Placebo Comparator: Cohort 4: Placebo<br>N=2, matching placebo, powder and solvent for oral solution, single dose | Drug: Placebo<br>* Matching placebo: powder and solvent for oral suspension<br>|
| Experimental: Cohort 5: 2000mg BTZ-043 fasting<br>N=8, 2000 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose | Drug: BTZ-043<br>* Powder and solvent for oral suspension<br>|
| Placebo Comparator: Cohort 5: Placebo<br>N=2, matching placebo, powder and solvent for oral solution, single dose | Drug: Placebo<br>* Matching placebo: powder and solvent for oral suspension<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events concerning ECG as assessed by CTCAE v4.03 (Common Terminology Criteria for Adverse Events) | Measured by 12-lead ECG assessments on 6 different timepoints. | 0.5 hours to 12.0 hours post-dosing | 
| Number of participants with treatment-related adverse events concerning safety laboratory as assessed by CTCAE v4.03 | Measured by clinical chemistry, haematology, coagulation, urinalysis on 2 different timepoints | 24 hours to 26 hours post-dosing | 
| Number of participants with treatment-related adverse events concerning vital signs as assessed by CTCAE v4.03 | Measured by blood pressure, pulse rate, respiratory rate and tympanic body temperature on 7 different timepoints | 0.25 hours to 48 hours post-dosing | 
| Number of participants with treatment-related adverse events concerning clinical observations as assessed by CTCAE v4.03 | Examination of general appearance, skin, neck (including thyroid), throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular and neurological systems. | 4 hours to 48 hours post-dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic assessment of BTZ-043 after a single oral dose | Blood samples for the determination of Area under the plasma concentration versus time curve (AUC) will be assessed in BTZ-043 and the metabolites BTZ-045S and M2 | 0.25 hours to 36 hours post-dosing | 
| Pharmacokinetic assessment of BTZ-043 after a single oral dose | Blood samples for the determination of Peak Plasma Concentration (Cmax) will be assessed in BTZ-043 and the metabolites BTZ-045S and M2 | 0.25 hours to 36 hours post-dosing | 
| Determining the effect of sex differences on systemic exposure by analyzing the PK of BTZ-043 in male and female participants. | Estimated via comparison of the exposure (AUC0-inf) of BTZ-043 in males and females | 0.25 hours to 36 hours post-dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Anti-Bacterial Agents, Respiratory Tract Infections