A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose (SAD) Study Including a Food Interaction Study, Followed by a Multiple Ascending Dose (MAD) Study to Evaluate the Safety, Tolerability and Pharmacokinetics Profile of MT101-5 in Healthy Volunteers
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Mthera Pharma Co., Ltd.
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Apparent Volume of distribution (Vz/F)
Overview
Brief Summary
The primary study objective is to establish the safety and tolerability of MT101-5 after a single and multiple dose administrations in healthy volunteers. The safety and overall tolerability of MT101-5 will be evaluated based on:
- Incidence of Dose Limiting Toxicities (DLTs)
- Incidence of Treatment-Emergent Adverse Events (TEAEs).
- Incidence of withdrawals due to Adverse Events (AEs).
- Change/shifts in laboratory values. Change in vital signs.
- Change in Electrocardiogram (ECG) parameters.
- Changes in physical examination findings
Detailed Description
SAD Phase including Food Interaction:
Subjects will be assigned to one of up to five MT101-5 treatment cohorts and will be randomly assigned 6:2 within their cohort to receive MT101-5 or placebo. On Day 1, following an overnight fast of at least 10 hours, the randomly assigned dose of MT101-5 or placebo will be administered as oral tablet in a fasting state with 240 mL (i.e., 8 fluid ounces) of water. Additional water is permitted ad lib except for the period 1 hour before to 1 hour after administration of the drug product. No food is allowed for at least 4 hours after the dose. Subjects should receive standardized meals scheduled at the same time throughout the study.
For the Food Interaction phase, on Day 1 following an overnight fast of at least 10 hours, the study subjects should start their standardized high-fat breakfast meal 30 minutes before administration of the drug product. Trial subjects should eat this meal in 30 minutes or less. Subjects will be administered MT101-5 or placebo as an oral tablet 30 minutes after start of intake of a standardized high-fat breakfast with 240 mL (8 fluid ounces) of water. Additional water is allowed ad lib except for 1 hour before and 1 hour after drug administration. No food is allowed for at least 4 hours after the dose.
MAD Phase:
Subjects will be randomly assigned 6:2 to receive MT101-5 or placebo once daily for 7 days. On Day 1, following an overnight fast of at least 10 hours, the randomly assigned dose of MT101-5 or placebo will be administered as oral tablet in a fasting state with 240 mL (i.e., 8 fluid ounces) of water. Additional water is permitted ad lib except for the period 1 hour before to 1 hour after administration of the drug product. No food is allowed for at least 4 hours after the dose. Subjects should receive standardized meals scheduled at the same time throughout the study. The same will be followed for days 2-7.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Care Provider)
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Subjects will be eligible for enrollment in the study only if they meet ALL of the following criteria:
- •SAD \& Food Interaction: Healthy male and female subjects, 18 to 45 years of age, inclusive.
- •MAD: Elderly healthy male and female subjects ≥ 65 years of age
- •SAD \& Food Interaction: The subject has a body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive, and weighs at least 50 kg.
- •MAD: The subject has a body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and weighs at least 50 kg.
- •The subject is in good health and has no medical condition of clinical significance or that may impact the outcome of the study, as determined by the investigator (as determined by medical history, physical examination, 12-lead electrocardiogram \[ECG\], vital signs, and clinical laboratory results at screening).
- •The subject is able to understand the nature of the study and any potential hazards associated with participating in it.
- •The subject is able to communicate satisfactorily with the investigator and to participate in, and comply with, the requirements of the study.
- •The subject is willing to provide written informed consent to participate in the study after reading the informed consent form and the information provided and has had the opportunity to discuss the study with the investigator or designee.
- •Negative pregnancy test for female subjects of childbearing potential. Women of childbearing potential (WOCBP) and Women of non-childbearing potential are eligible to participate. Both women of childbearing potential and women of non-childbearing potential should use an approved method of birth control and agrees to continue to use this method for the duration of the study (and for 90 days after taking the last dose of MT101-5).
Exclusion Criteria
- •Subjects will be eligible for enrollment in the study only if they meet NONE of the following criteria:
- •The subject has a history of severe allergic or anaphylactic reactions.
- •The subject has a known allergy or hypersensitivity to any component of the formulation.
- •The subject has a medical history or current evidence of any clinically significant (as determined by the investigator) cardiac, endocrine (including diabetes), hematologic, hepatobiliary (abnormal alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], gamma-glutamyl transpeptidase \[GGT\], or total bilirubin), immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal condition, or other major disease.
- •The subject has a history of any malignant disease.
- •The subject has a history of more than one herpes zoster episode or multimetameric herpes zoster.
- •The subject has a history of an opportunistic infection (e.g. cytomegalovirus, pneumocystis carinii, aspergillosis, clostridium difficile).
- •The subject has a history of or ongoing chronic or recurrent infectious disease (e.g. infected indwelling prosthesis, osteomyelitis, chronic sinusitis).
- •The subject has had major trauma or surgery in the 2 months before screening or at any time between screening and check-in.
- •The subject has had an acute infection within 2 weeks before screening or at any time between screening and check-in including, but not limited to, history, signs, or symptoms of a common cold (e.g., mild rhinorrhea), untreated oral/dental abnormalities (e.g. untreated dental caries as determined by examination of the mouth), or untreated disruption of the skin.
Arms & Interventions
SAD Phase
SAD Phase: including Food Interaction - Blinding and Randomization: This is a randomized, double-blind, placebo-controlled, sentinel design, dose-escalating study with 40 healthy volunteers. Subjects will be assigned to 1 of up to 5 cohorts and will be randomized within each cohort to MT101-5 or placebo, as follows:
- cohort 1: 100 mg (8 subjects total; 6 receiving MT101-5, 2 receiving placebo)
- cohort 2: 150 mg (8 subjects total; 6 receiving MT101-5, 2 receiving placebo)
- cohort 3: 300 mg (8 subjects total; 6 receiving MT101-5, 2 receiving placebo)
- cohort 4: 450 mg (8 subjects total; 6 receiving MT101-5, 2 receiving placebo)
- cohort 5: 600 mg (8 subjects total; 6 receiving MT101-5, 2 receiving placebo)
Intervention: MT101-5 (Drug)
Food Interaction Phase
Food Interaction Phase: Following the completion of the SAD phase, if study stopping criteria (SSC) is not met, then subjects in cohort 5 will cross-over to the fed part of the study following a 7 day washout period. If SSC is achieved in the SAD phase, then the previous dose will be in the Food Interaction phase.
Intervention: MT101-5 (Drug)
MAD Phase
MAD Phase; Blinding and Randomization: This is a randomized, double-blind, placebo-controlled study in approximately 8 elderly healthy volunteers. If study stopping criteria (SSC) is not met in the SAD phase, then subjects will be assigned to the cohort 5 dose. If SSC is achieved in the SAD phase, then the previous dose will be used as the cohort in the MAD phase
Intervention: MT101-5 (Drug)
Outcomes
Primary Outcomes
Apparent Volume of distribution (Vz/F)
Time Frame: 0-96 hours
ECG ventricular rate (beats per minute)
Time Frame: On day 7 after the last study drug administration
QRS interval (msec)
Time Frame: On day 7 after the last study drug administration
Area under the plasma drug concentration-time curve (AUC)
Time Frame: 0-96 hours
Incidence of withdrawals due to Adverse Events (AEs)
Time Frame: Day 1 through 7 days after the last study drug administration
Incidence of withdrawals due to Adverse Events (AEs) defined above
Change in comprehensive metabolic panel test
Time Frame: Change from baseline to day 7 after the first study drug administration
Change of respiratory rate
Time Frame: Change from pre-dose to day 7 after the last study drug administration
PR interval (msec)
Time Frame: On day 7 after the last study drug administration
Maximum observed plasma drug concentration (Cmax)
Time Frame: 0-96 hours
Apparent terminal elimination half-life (t1/2)
Time Frame: 0-96 hours
Incidence of Dose Limiting Toxicities (DLTs)
Time Frame: Day 1 through 7 days after the last study drug administration
Any clinically significant adverse event (AE)/serious adverse event (SAE) or clinically significant laboratory abnormality which is classified as \> Grade 2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0), where applicable, deemed by the investigator as at least "possibly, probably or definitely related" to the drug but unrelated to concurrent illness, or concomitant medications.
Change of blood pressure (both systolic and diastolic blood pressures)
Time Frame: Change from pre-dose to day 7 after the last study drug administration
Time to maximum observed plasma drug concentration (Tmax)
Time Frame: 0-96 hours
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Day 1 through 7 days after the last study drug administration
An adverse event (AE) is defined as any unfavorable or unintended sign, symptom, or disease that occurs or is reported by the patient to have occurred, or a worsening of a pre-existing condition. An adverse event may or may not be related to the study treatment.
Change in complete blood count test
Time Frame: Change from baseline to day 7 after the first study drug administration
Change in urinalysis test
Time Frame: Change from baseline to day 7 after the first study drug administration
Change in pregnancy test
Time Frame: Change from baseline to day 7 after the first study drug administration
Change of pulse
Time Frame: Change from pre-dose to day 7 after the last study drug administration
Change of temperature
Time Frame: Change from pre-dose to day 7 after the last study drug administration
QT interval (msec)
Time Frame: On day 7 after the last study drug administration
QTc interval (msec)
Time Frame: On day 7 after the last study drug administration
Percentage of AUC0-∞ extrapolated from Tlast to infinity (AUCext)
Time Frame: 0-96 hours
Apparent plasma clearance (CL/F)
Time Frame: 0-96 hours
Secondary Outcomes
No secondary outcomes reported