Pain
Conditions
Brief summary
Primary Objective: To determine the safety and tolerability of single and multiple ascending oral doses of MEB-1170 in healthy subjects. Secondary Objectives: 1. To determine the single and multiple oral dose pharmacokinetic profiles of MEB-1170 and the primary metabolite, M373, in healthy subjects. 2. To determine the effect of food on the pharmacokinetic (PK) profile of a single oral dose of MEB-1170 in healthy subjects. 3. To assess the pharmacodynamic (PD) response following single and multiple oral doses of MEB-1170
Detailed description
Study Design: This will be a double-blind, placebo-controlled, single and multiple oral dose study conducted in two parts: Part A: SAD+FE: Part A will comprise a single ascending dose (SAD), sequential cohort study, incorporating a food effect (FE) evaluation. Up to 40 subjects will be studied in 5 cohorts (Cohorts A1 to A5), each cohort consisting of 8 subjects (6 treated with MEB-1170, 2 treated with placebo). Subjects in Cohorts A1, A2, A4 and A5 will participate in 1 treatment period only, residing at the CRU from Day -1 (the day before dosing) to Day 3 (48 hours postdose). Subjects in Cohort A3 will participate in 2 treatment periods (once in fasted state, once in fed state) separated by a minimum of 6 days. All subjects will return for a poststudy visit approximately 5 to 7 days after their final dose. Each Cohort will include sentinel dosing such that two subjects (one active and one placebo) will be dosed at least 48 hours before the remaining subjects in the cohort. Continuation to dose the remaining subjects will be at the Investigator's discretion, in consultation with the Sponsor. All doses will be administered in accordance with a randomization schedule in the fasted state in the morning of Day 1, except for Cohort A3 Treatment Period 2 where MEB-1170 will be given 30 minutes after start of a high fat breakfast (see below). Each subject in Cohorts A1, A2, A4 and A5 will receive only a single dose of MEB-1170 or placebo during the study. Subjects in Cohort A3 will participate in a 2-period treatment design in which they will be assessed for both the single-dose of MEB-1170 in a Fed and in a Fasted condition. Subjects will receive the same treatment (ie, either MEB-1170 or placebo) in both Period 1 and Period 2, and thus subjects will receive either two single doses of MEB-1170 or two single doses of placebo during the study. Fasting state assessments will occur in Period 1 and Fed state assessments in Period 2. SAD Assessments: * Safety/tolerability throughout study * Physical examination, vital signs, clinical laboratory findings, and ECG * PK concentrations * PD assessments (pupillometry, capnography, oximetry, cold pressor testing) Following the completion of each cohort, a safety and tolerability review will be conducted by the Safety Review Committee (SRC; see below) prior to proceeding to the next cohort. Based on this review, a decision may be made to continue the study as planned, repeat the same dose in another Cohort, assess a lower dose, add an intermediate dose, or terminate the study. Additionally, if no dose limiting toxicities are seen, further cohorts at higher doses may be added. Part B: MAD: Part B will comprise a multiple ascending dose (MAD), sequential cohort study. This part will be initiated after the first three SAD cohorts have been fully evaluated for safety and tolerability and the SRC has concluded that the MAD portion may commence. Up to 32 subjects will be studied in 4 cohorts (Cohorts B1 to B4), each cohort consisting of 8 subjects. In each of Cohorts B1 to B4, 6 subjects will receive MEB-1170 and 2 will receive placebo. Once-daily dosing will occur on Days 1 to 7, inclusive, for all subjects. Each subject will participate in 1 treatment period only, residing at the CRU from the evening of Day -1 (the day before dosing) until the morning of Day 9 (48 hours after the final dose on Day 7). All subjects will return for a poststudy visit 6 to 8 days after their final dose for a final safety assessment. Dose levels to be studied will be determined following review of data from Part A. Following completion of each cohort in Part B, a safety and tolerability review will be conducted by the SRC prior to proceeding to the next cohort (see below). Based on this review, a decision may be made to continue the study as planned, repeat the same dose in another Cohort, assess a lower dose, add an intermediate dose or terminate the study. Additionally, if no dose limiting toxicities are seen, further cohorts at higher doses may be added. MAD Assessments: * Safety/tolerability throughout study * Physical examinations, vital signs, clinical laboratory findings, and ECG * PK concentration (see Schedule of Assessments for details) * PD assessments (pupillometry, capnography, cold pressor testing, oximetry) Reference Therapy, Dose and Mode of Administration: Matching placebo capsule administered orally.
Interventions
DRUGMEB-1170
Depending on the dosage, either 20 mg, 40 mg capsules, or a combination of both
DRUGPlacebo
Equivalent number and size of capsules containing placebo
Sponsors
Mebias Discovery, Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
Double Blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
To be eligible for this study, subjects must meet all of the following inclusion criteria: 1. Provides written IRB-approved informed consent prior to any study procedures. 2. Male or female between 18 and 55 years old (inclusive) at the time of screening. 3. In good general health at screening, free from clinically significant unstable medical, surgical or psychiatric illness, at the discretion of the Investigator. 4. Subjects have a BMI between ≥ 18.0 and ≤ 32.0 kg/m2 at screening. 5. Vital signs (measured in supine position after a 5-minute rest) at screening: 1. Systolic blood pressure ≥90 and ≤140 mmHg 2. Diastolic blood pressure ≥50 and ≤ 90 mmHg 3. Heart rate ≥45 and ≤100 bpm 4. Temperature ≥35.5 °C and ≤ 37.5 °C 5. Vital signs may be repeated once, within a minimum of 10 minutes of the completion of the last set of vital signs (while maintaining supine position until the repeated set of vital signs are collected), if it is suspected that falsely high or low levels have been obtained. 6. Adequate venous access to allow collection of multiple blood samples. 7. Negative Covid PCR test upon admission to the CRU. a. Subjects in Cohort A3 will need a second COVID test prior to admission the CRU for Period 2. 8. No relevant dietary restrictions and willingness to consume standard meals and snacks. 9. Willing to comply with all study procedures and requirements 10. Ability to tolerate the cold pressor test (determined at screening) 11. Women of childbearing potential (WOCBP) must be non-pregnant and non-lactating, and must use two acceptable, highly effective methods of contraception from screening until study completion, including the follow-up period (please see Section 9.4.2 for acceptable methods of contraception). Abstinence as a lifestyle choice is also acceptable. WOCBP must have a negative serum pregnancy test at Screening and negative urine pregnancy test at Day -1 and be willing to have additional pregnancy tests as required throughout the study. WOCBP must also use two acceptable, highly effective methods of contraception from screening until study completion, including the follow-up period and for 30 days after the last dose (please see Section 10.4.2 for acceptable methods of contraception). Women not of childbearing potential must be post menopausal for ≥12 months or be surgically sterile. Hysterectomy with retention of ovary function is permitted. Post-menopausal status will be confirmed through testing of FSH levels ≥ 40 IU/mL at screening for amenorrhoeic female subjects. 12. Male subjects must be surgically sterile (\> 30 days since vasectomy per medical history or verbal confirmation), or, if engaged in sexual relations with a WOCBP, the subject and his partner must use two acceptable, highly effective methods of contraception from screening until study completion, including the follow-up period and 30 days after the last dose (please see Section 9.4.2 for acceptable methods of contraception). Abstinence as a lifestyle choice is also acceptable.
Exclusion criteria
To be eligible for this study, subjects must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Single and Multiple Ascending Doses of MEB-1170 assess subjects with a physical exam | Through study completion, approximately 12 months | Complete physical examinations will be performed by a licensed physician, nurse practitioner or physician's assistant at the time points specified in the study schedules to ensure there are no changes compared to baseline assessment physical exams. |
| Safety and Tolerability of Single Ascending Doses of MEB-1170 for Fasting SAD and MAD laboratory assessments for blood chemistry | Through study completion, approximately 12 months | Biochemistry parameters to be tested - Glucose (GLU) (fasting labs only) |
| Safety and Tolerability of Single and Multiple Ascending Doses of MEB-1170 including clinical laboratory assessments for hematology | Through study completion, approximately 12 months | Hematology parameters to be tested are: • Hemoglobin (HGB) |
| Safety and Tolerability of Single and Multiple Ascending Doses of MEB-1170 including clinical laboratory assessments for blood chemistry | Through study completion, approximately 12 months | Biochemistry parameters to be tested are: • C-reactive protein (CRP) |
| Safety and Tolerability of Single and Multiple Ascending Doses of MEB-1170 including clinical laboratory assessments for urine | Through study completion, approximately 12 months | Macroscopic urinalysis parameters to be tested - pH (PH) |
| Safety and Tolerability of Single and Multiple Ascending Doses of MEB-1170 assessed by ECG | Through study completion, approximately 12 months | A 12-lead ECG will be taken at the time points delineated in the study schedules. Additional ECG monitoring may be performed at other times if deemed necessary. Note that triplicate ECGs are required during SAD, while single ECGs are required during MAD. Readout QT |
| Safety and Tolerability of Single and Multiple Ascending Doses of MEB-1170 to assess adverse events | Through study completion, approximately 12 months | Occurrence of all adverse events from first dose through end of study treatment and follow-up last visit will be monitored and treated as adverse events. |
| Safety and Tolerability of Single and Multiple Ascending Doses of MEB-1170 to assess suicidality risk | Through study completion, approximately 12 months | Utilize C-SSRS to assess suicidality risks. Performed at screening and in both SAD and MAD |
| Safety and Tolerability of Single and Multiple Ascending Doses of MEB-1170 assess vital signs | Through study completion, approximately 12 months | Vital sign of oral body temperature will be measured at the time points specified in the study schedules with subjects resting for at least 5 minutes in a supine position. When the time of vital signs measurement coincides with a blood draw, the vital signs will be taken before the scheduled blood draw where possible while ensuring the blood draw is within the window specified in the protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To determine the single and multiple oral dose pharmacokinetic profiles of MEB-1170 and the primary metabolite, M373, in healthy subjects - Cmax | Through study completion, approximately 12 months | To evaluate the pharmacokinetics of single and multiple doses of MEB-1170 Pharmacokinetic parameters including, but not limited to maximum plasma concentration (Cmax) SAD phase, * Day 1 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, and 16 hours * Day 2, 24 hours * Day 3, 48 hours MAD phase * Day 1 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, and 16 hours * Day 2, 24 hours (immediately pre-dose) * Day 3, immediately pre-dose * Day 4, immediately pre-dose * Day 5, immediately pre-dose * Day 6, immediately pre-dose * Day 7, immediately pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, and 16 hours * Day 8: 24 hours and 36 hours post-Day 7 dose * Day 9: 48 hours post-Day 7 dose |
| To determine the effect of food on the pharmacokinetic (PK) profile of a single oral dose of MEB-1170 in healthy subjects - AUC | Through study completion, approximately 12 months | To evaluate the pharmacokinetics of single and multiple doses of MEB-1170 Pharmacokinetic parameters including, but not limited to area under the plasma concentration-time curve (AUC) from 0 to 24hours (AUC0-24) * Day 1 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, and 16 hours * Day 2, 24 hours * Day 3, 48 hours |
| To determine the effect of food on the pharmacokinetic (PK) profile of a single oral dose of MEB-1170 in healthy subjects - Cmax | Through study completion, approximately 12 months | To evaluate the pharmacokinetics of single and multiple doses of MEB-1170 Pharmacokinetic parameters including, but not limited to maximum plasma concentration (Cmax) SAD phase, * Day 1 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, and 16 hours * Day 2, 24 hours * Day 3, 48 hours |
| To assess the pharmacodynamic (PD) response of Pupillometry following single and multiple oral doses of MEB-1170 | Through study completion, approximately 12 months | Pupil size and reactivity will be measured using a pupillometer device such as the NeuroOptics NPi-300 pupillometer. All pupillometer measurements will be made in the same windowless room, using standardized dim lighting. SAD: Check-in, immediately before dosing (t = 0) and at 3, 6, and 9 hours post-dose. MAD Day -1 and then on Days 2, 4, and 6, at hours \ t = 3, 6, and 9 post-dose. |
| To assess the pharmacodynamic (PD) response using capnography following single and multiple oral doses of MEB-1170 | Through study completion, approximately 12 months | EtCO2 will be measured in millimeters of mercury (mm Hg) using noninvasive capnography. A Masimo/Philips EMMA® Capnograph (Americas Headquarters: Masimo Corporation, 52 Discovery, Irvine, CA 92618, USA) will be used with an airway adapter and subject mouthpiece. The EMMA Capnograph provides clear, continuous capnograph of carbon dioxide values, is simple, easy-to-use, with audible and visual alarm system for No Adapter, Clogged Adapter, No Breath (Apnea), Low Battery and adjustable High and Low EtCO2 alarm. Subjects will be instructed to breathe normally through the mouthpiece for 1 minute (according to the instructions provided with the capnograph). SAD: Check-in, immediately before dosing (t = 0) and at 3, 6, and 9 hours post-dose. MAD: Day -1 and then on Days 2, 4, and 6, at hours \ t = 3, 6, and 9 post-dose. |
| To assess the pharmacodynamic (PD) response using oximetry following single and multiple oral doses of MEB-1170 | Through study completion, approximately 12 months | Oximetry measures oxygen saturation of circulating blood (SpO2). Measurements should be performed using the same finger during the course of the subjects' participation. For each time point indicated, a single SpO2 measure will be recorded. SAD: Check-in, immediately before dosing (t = 0) and at 3, 6, and 9 hours post-dose. MAD: Day -1 and then on Days 2, 4, and 6, at hours \ t = 3, 6, and 9 post-dose. |
| To assess the pharmacodynamic (PD) effect of analgesia using a Cold Pressor Test following single and multiple oral doses of MEB-1170 | Through study completion, approximately 12 months | Subjects will be asked to place their left hand and forearm into an apparatus containing an ice bath, with the instruction to remove the arm from the water when they can no longer tolerate it. The upper limit for the duration of the test, which will not be communicated to the subjects, will be 5 minutes (300 seconds). SAD: 4.5 and 8.5 hours post-dose. MAD:Days 1, 3, and 5 at \ t = 3 hours post-dose. |
| To determine the single and multiple oral dose pharmacokinetic profiles of MEB-1170 and the primary metabolite, M373, in healthy subjects - AUC | Through study completion, approximately 12 months | To evaluate the pharmacokinetics of single and multiple doses of MEB-1170 Pharmacokinetic parameters including, but not limited to area under the plasma concentration-time curve (AUC) from 0 to 24hours (AUC0-24) SAD phase, * Day 1 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, and 16 hours * Day 2, 24 hours * Day 3, 48 hours MAD phase * Day 1 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, and 16 hours * Day 2, 24 hours (immediately pre-dose) * Day 3, immediately pre-dose * Day 4, immediately pre-dose * Day 5, immediately pre-dose * Day 6, immediately pre-dose * Day 7, immediately pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, and 16 hours * Day 8: 24 hours and 36 hours post-Day 7 dose * Day 9: 48 hours post-Day 7 dose |
Countries
United States
Contacts
Primary ContactBarbara Lomeli, MD, CPI
Backup ContactSunu Valasseri, MBBS, MSc, DPM
Outcome results
None listed