A Single Ascending Dose Study of BTZ043

Michael Hoelscher

Status and phase: Completed; Phase 1

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

Treatments: Drug: Placebo; Drug: BTZ-043

Study type: Interventional

Funder types: Other

Identifiers

NCT03590600

LMU-IMPH-BTZ043-01

Details and patient eligibility

About

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).

Enrollment: 30 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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30 participants in 10 patient groups, including a placebo group

Cohort 1: 125 mg BTZ-043 fasting

Experimental group

Description:

N=8, 125 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose

Treatment:

Drug: BTZ-043

Cohort 1: Placebo

Placebo Comparator group

Description:

N=2, matching placebo, powder and solvent for oral solution, single dose

Treatment:

Drug: Placebo

Cohort 2: 250 mg BTZ-043 fasting

Experimental group

Description:

N=8, 250 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose

Treatment:

Drug: BTZ-043

Cohort 2: Placebo

Placebo Comparator group

Description:

N=2, matching placebo, powder and solvent for oral solution, single dose

Treatment:

Drug: Placebo

Cohort 3: 500 mg BTZ-043 fasting

Experimental group

Description:

N=8, 500 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose

Treatment:

Drug: BTZ-043

Cohort 3: Placebo

Placebo Comparator group

Description:

N=2, matching placebo, powder and solvent for oral solution, single dose

Treatment:

Drug: Placebo

Cohort 4: 1000 mg BTZ-043 fasting

Experimental group

Description:

N=8, 1000 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose

Treatment:

Drug: BTZ-043

Cohort 4: Placebo

Placebo Comparator group

Description:

N=2, matching placebo, powder and solvent for oral solution, single dose

Treatment:

Drug: Placebo

Cohort 5: 2000mg BTZ-043 fasting

Experimental group

Description:

N=8, 2000 mg BTZ-043 fasting, oral administration, powder and solvent for oral suspension, single dose

Treatment:

Drug: BTZ-043

Cohort 5: Placebo

Placebo Comparator group

Description:

N=2, matching placebo, powder and solvent for oral solution, single dose

Treatment:

Drug: Placebo