Safety, Tolerability, and Pharmacokinetics of Oral BT-11 in Healthy Adult Male and Female Volunteers
Study Details
Study Description
Brief Summary
Study type: Interventional Description of intervention(s) / exposure
For single ascending dose, five dose target ranges of BT-11 (depending on body weight the doses in each cohort will be 5.9 - 7.7 mg/kg; 18.9 - 25.0 mg/kg; 44.3 - 50.0 mg/kg; 68.5 - 75 mg/kg and 94.2 - 100.0 mg/kg) will be evaluated, based on subject's weight on Day 1.
For multiple ascending dose (once daily for 7 days), three dose target ranges of BT-11 (depending on body weight the doses in each cohort will be 5.9 - 7.7 mg/kg; 44.3 - 50.0 mg/kg; and 94.2 - 100.0 mg/kg) will be evaluated, based on subject's weight on Day 1.
White tablets containing 500 mg BT-11 or matching placebo tablets will be dispensed.
Single ascending dose duration of administration will be once. For multiple ascending dose it will be up to 7 days.
The mode administration will be oral tablet. Compliance and adherence to the intervention will be performed based on the tablet return, tablet not consumed by the subject.
The safety monitoring committee will evaluate safety at conclusion of single ascending cohort 2 prior to the commencement of dosing for the multiple ascending dose.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Primary outcome: To assess the safety and tolerability of BT-11 after single and multiple ascending oral dose administration in healthy volunteers
The safety and tolerability profile of BT-11 as evidenced by the occurrence, timing, frequency, and severity of adverse events (AE) and clinically significant:
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laboratory abnormalities Haematology, Coagulation, Serum Chemistry, Urinalysis, HIV, HBsAg, HCV
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physical exam findings Complete physical exam include, at a minimum, assessment of the following systems: skin, head, ears, eyes, nose and throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system
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12-lead ECG aberrations ECG data (RR, PR, QRS, QT and QTcF intervals and pulse rate)
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and/or vital signs abnormalities Vital signs assessments will include systolic and diastolic blood pressure, pulse, tympanic body temperature, and respirations
Timepoint: Adverse events will be recorded from the time of first dosing through to end of study date.
Laboratory abnormalities at the screening visit, up to 28 days prior to the first dose of study medication then up to end of study visit.
Physical Exam findings will be collected at screening, Day-1 and Day 2 for the single ascending dose. For multiple ascending dose it will be collected at screening, Day-1, Day 3, Day 5 and Day 7
12-lead ECG aberrations will be collected from Screening then on Day -1 and Day 2 for the single ascending dose. For MAD it will be collected at screening, Day-1, Day 3, Day 5 and Day 7
Vital signs abnormalities collected from Screening then on Day -1 and Day 2 for the single ascending dose. For MAD it will be collected at screening, Day-1, Day 3, Day 5 and Day 7
Primary outcome: To assess the safety and tolerability of BT-11 after single and multiple ascending oral dose administration in healthy volunteers.
Timepoint: For single ascending dose blood samples for PK analysis will be collected pre-dose and at 15, 30, 45 minutes, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Urine samples for PK analysis will be collected pre-dose and 0-24 hours post-dose;
For multiple ascending blood samples for PK analysis will be collected pre-dose and at 15, 30, and 45 min and 1, 1.25 1.5, 2, 3, 4, 6, 8, 10, 12 and 18 hours post Day 1 dose. Pre-dose on Day 2
Urine samples for PK analysis will be collected on Day 1, pre-dose and at 0-24 hours post-dose
On follow up period, Day 3 to Day 6, Plasma samples for PK analysis will be collected pre-dose on each day.
Secondary outcome: The following PK parameters will be determined:
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Time to maximum concentration (tmax);
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Maximum concentration (Cmax);
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Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-tlast);
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Area under the concentration-time curve from time 0 to infinity (AUC0-inf);
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Terminal Elimination Rate Constant (kel);
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Terminal half-life (t1/2);
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Terminal clearance (CL/F);
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Volume of distribution (Vd/F).
Timepoint: The following PK parameters will be determined for single ascending dose:
Area under the concentration-time curve from time 0 to 24 hours from start of first dose (AUC0-24h);
• Amount of drug excreted in urine in each collection interval
For the multiple ascending dose:
Area under the concentration-time curve from time 0 to 24 hours from start dosing (AUC0-24h) on Day 1 and 0 to 24 hours (AUC0-24h) following the last dose on Day 7;
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Pre-dose trough on Days 2, 3, 4, 5 and 6;
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Amount of drug excreted in urine in each collection interval;
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Volume of distribution at steady state (Vss/F).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo
|
Drug: BT-11 Placebo
BT-11 Placebo (Finished Product),
|
| Experimental: BT-11
|
Drug: BT-11 Active
BT-11 active - 500 mg Oral Tablets
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-related adverse events [up to 14 days]
- Number of participants with physical examination findings [up to 7 days]
- Change from baseline in QTcF interval [up to 7 days]
- Change from baseline in blood pressure [up to 7 days]
Secondary Outcome Measures
- Maximum plasma concentration [Cmax] [up to 72 hours]
- Area under the plasma concentration versus time curve [AUC] [up to 72 hours]
- Plasma half-life [Thalf] [up to 72 hours]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy male and female volunteers aged 18 to 65 years, inclusive.
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Body weight 65 - 85 kg.
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Body Mass Index (weight in kg divided by square of height in meters) 19-31 kg/m2, inclusive.
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Male volunteers must agree to abstain, between dosing and 30 days post-dosing, from sexual intercourse with pregnant or lactating women and, if sexually active with a female partner, to use a condom in addition to his female partner's use of another form of contraception (e.g., IUD, diaphragm, oral contraceptive, injectable progesterone contraceptive, subdermal implant contraceptive, or tubal ligation). A male practicing abstinence is also acceptable.
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Female subjects of child-bearing potential, with a fertile male sexual partner, should be willing to use adequate contraception from Day 1 until 30 days after the follow-up visit. Adequate contraception is defined as an intrauterine device combined with at least one of the following forms of contraception: a diaphragm or cervical cap, or a condom. Also, total abstinence, in accordance with the lifestyle of the subject, is acceptable.
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Volunteer agrees not to take any concomitant medications, including prescriptions or over-the-counter (OTC) medications during the interval from 3 days prior to dosing until after the last PK blood draw for the study.
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Volunteer agrees not to consume alcohol during the interval from 3 days prior to dosing until after the last PK blood draw for the study.
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Volunteer is able to communicate effectively with study personnel.
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Volunteer is able to understand and comply with protocol and investigative site requirements, instructions, and restrictions.
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Volunteer has read, confirmed understanding of, and signed the written informed consent form after the nature of the study and all essential elements of the informed consent document have been fully explained and all of the Volunteer's questions have been answered to his or her satisfaction, prior to initiation of any study procedures.
Exclusion Criteria:
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Any clinically significant abnormality identified in the screening history, physical examination (including Vital Signs), laboratory testing, or electrocardiographic testing. Repeat testing of vital signs to confirm the value is allowed. Up to two repeat tests are permitted to confirm eligibility.
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An excessive fall in blood pressure on orthostatic testing at screening or Day -1 (i.e., a fall in systolic blood pressure > 25 mmHg or in diastolic blood pressure > 15 mmHg).
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Any 12-lead ECG finding at screening or on Day -1 that may, in the opinion of the Investigator, compromise interpretation of ECGs for cardiac safety assessment or complicate interpretation of events that may occur post-dose (e.g., QT not accurately measurable, conduction abnormalities)
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Positive test for HIV, hepatitis B surface antigen, or hepatitis C antibody.
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Any clinically significant cardiac, pulmonary, renal, metabolic, neurologic, or other medical, behavioural, or genetic condition.
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Any condition that places the volunteer at significantly increased risk or may risk compromise of study objectives.
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Use of prescription or non-prescription drugs 3 days or 5 half-lives (whichever is longer) prior to dosing to after last PK draw.
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Use of herbal supplements within 3 days or 5 half-lives (whichever is longer) prior to the first dose of study drug to after last PK draw.
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Use of alcohol within 72 hours prior to first dose of study drug.
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History of drug or alcohol abuse (by DSM-IV definition) within 3 months prior to screening.
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Positive urine drug screen (including cotinine, cannabis, cocaine, opiates, amphetamines, and other tests as determined by Investigator). Repeating analyses will be allowed if the PI suspects that there might be false positive results.
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Volunteer has a contraindication to blood sampling or is considered to have insufficient peripheral venous access.
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Volunteer has donated blood or blood products in volumes of 450 mL or more within 30 days prior to study enrollment.
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Volunteer has been previously exposed to BT-11.
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Volunteer has participated in a study of any investigational drug, device, biologic, or other agent within 30 days prior to study enrollment.
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Volunteer has known hypersensitivity to BT-11 or any of its constituents.
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Volunteer has any disorder (e.g., psychiatric, addictive) that, in Investigator's judgement, may compromise his/her ability to provide legal written informed consent.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Landos Biopharma Inc. | Blacksburg | Virginia | United States | 24060 |
Sponsors and Collaborators
- Landos Biopharma Inc.
Investigators
- Study Director: Simon Lichtiger, MD, Landos Biopharma
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BT-11-1a