Clinical trial NCT03590600: A Single Ascending Dose Study of BTZ043
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tuberculosis
Tuberculosis, Pulmonary
Bacterial Infections
Lung Diseases
Mycobacterium Infections
Keywords: Phase 1
Anti-Bacterial Agents
Respiratory Tract Infections
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
Collaborators: name: German Center for Infection Research
name: German Federal Ministry of Education and Research
name: Hans Knöll Institute (HKI)
First posted: 2018-07-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with treatment-related adverse events concerning ECG as assessed by CTCAE v4.03 (Common Terminology Criteria for Adverse Events)
timeFrame: 0.5 hours to 12.0 hours post-dosing
measure: Number of participants with treatment-related adverse events concerning safety laboratory as assessed by CTCAE v4.03
timeFrame: 24 hours to 26 hours post-dosing
measure: Number of participants with treatment-related adverse events concerning vital signs as assessed by CTCAE v4.03
timeFrame: 0.25 hours to 48 hours post-dosing
measure: Number of participants with treatment-related adverse events concerning clinical observations as assessed by CTCAE v4.03
timeFrame: 4 hours to 48 hours post-dosing
Secondary outcomes:
measure: Pharmacokinetic assessment of BTZ-043 after a single oral dose
timeFrame: 0.25 hours to 36 hours post-dosing
measure: Pharmacokinetic assessment of BTZ-043 after a single oral dose
timeFrame: 0.25 hours to 36 hours post-dosing
measure: Determining the effect of sex differences on systemic exposure by analyzing the PK of BTZ-043 in male and female participants.
timeFrame: 0.25 hours to 36 hours post-dosing
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan
state: Bavaria
Study officials:
References: