A Single Ascending Dose Study of BTZ043

Sponsor

Michael Hoelscher (Other)

Overall Status

Completed

CT.gov ID

NCT03590600

Collaborator

German Center for Infection Research (Other), German Federal Ministry of Education and Research (Other), Hans Knöll Institute (HKI) (Other)

Enrollment

Location

Arms

8.9

Actual Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis Tuberculosis, Pulmonary Bacterial Infections Lung Diseases Mycobacterium Infections	Drug: BTZ-043 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Subjects, investigators and investigators' staff, persons performing the assessments or being responsible for determining dosing regimen/adjustments, and staff of the sponsor or data analysts, will remain blinded from the time of randomization until database lock, using the following methods: randomization data, including any documentation identifying the treatment allocation, are kept strictly confidential until the time of unblinding with the following exceptions: staff responsible for study drug management (i.e. the staff in the CRO CTS department preparing the IMP).

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 7, 2018

Actual Primary Completion Date :

Aug 14, 2018

Actual Study Completion Date :

Mar 5, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Pharmacokinetic assessment of BTZ-043 after a single oral dose [0.25 hours to 36 hours post-dosing]
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
Pharmacokinetic assessment of BTZ-043 after a single oral dose [0.25 hours to 36 hours post-dosing]
Blood samples for the determination of Peak Plasma Concentration (Cmax) will be assessed in BTZ-043 and the metabolites BTZ-045S and M2
Determining the effect of sex differences on systemic exposure by analyzing the PK of BTZ-043 in male and female participants. [0.25 hours to 36 hours post-dosing]
Estimated via comparison of the exposure (AUC0-inf) of BTZ-043 in males and females

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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