Clinical trial NCT06259903: Subcutaneous Administration of MD-18 in Healthy Subjects
Official title: A Single Center, Single Dose, Double-blind, Randomized, Placebo-Controlled, Dose-Escalating Study to Evaluate Safety, Tolerability and Pharmacokinetics of Subcutaneously Administered MD-18 in Healthy Subjects.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Cohen Global, Ltd.
Sponsor class: INDUSTRY
First posted: 2024-02-14
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Five subjects in cohort 1 will be administered a single subcutaneous dose of 40 mg MD-18 and two will receive placebo. The cohort will be staggered with 2 active and one placebo patient treated on day 1 and the remainder on Day 3 if there are no safety concerns. The same dosing regimen will be observed for each incremental cohort, with the remaining planned doses being 80, 160, 240 and 320 milligram (mg).
Primary purpose: TREATMENT

Brief summary: A Single Center, Single Dose, Double-blind, Randomized, Placebo-controlled Dose-Escalating Study to Evaluate Safety, Tolerability and Pharmacokinetics of Subcutaneously Administered MD-18 in healthy subjects.

Detailed description: This study will be conducted as a single-center study. A single escalating dose of MD-18 will be administered to each subject with a seven-day follow-up. 35 subjects will be enrolled. Cohorts will receive doses of 40. 80, 160, 240 or 320 milligram of MD-18 using 5:2 (active: placebo) randomization. Sentinel dosing will be used, consisting of enrolling three subjects at a 2:1 active to placebo ratio followed by the remaining subjects in the respective dose cohorts enrolled 48 hours later. Each of the 5 dose cohorts will enroll five active and two placebo subjects, with a total of 25 subjects receiving active therapy across the 5 arms and 10 subjects receiving placebo. The study will be conducted on an in-patient basis for the first 24 hours, followed by discharge and telephone check-in at 48 and 72 hours and return for follow-up visit at 7 days after administration of a single dose of MD-18.

Eligibility criteria: Inclusion Criteria:

1. Subjects aged 18-70 years, both genders.
2. Healthy as determined by a physician, based on history, medical examination, vital signs, laboratory tests, cardiac monitoring and respiratory function. History must comply with the following:

   1. Absence of clinically significant illness or surgery within the preceding 12 weeks.
   2. Absence of clinically significant history of neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and/or metabolic disease.
3. Male subjects with female partners of childbearing potential must agree to utilize an approved contraceptive during the study.
4. Female subjects of child-bearing potential with negative urine pregnancy tests and who agree to use contraception during the study.
5. Female subjects of non-child-bearing potential (i.e. tubal ligation, hysterectomy, or postmenopausal).
6. Body mass index (BMI) of 18.5-39.9 kg/m2

Exclusion Criteria:

1. History of excessive alcohol use (defined as \>21 drinks per week for males and \>14 drinks per week for females), recreational drug use or drugs of abuse within the past three months, or failure on urinary drug screen. Note: use of Cannabinoids for medical purposes is allowed.
2. Pregnant or breastfeeding within six months of screening assessment.
3. Substantial changes in eating habits or exercise routine within the preceding three months.
4. Evidence of eating disorders.
5. \>5% weight change in the past three months.
6. Bariatric surgery within the past five years.
7. Significant renal impairment glomerular filtration rate (GFR) \<60 milligram/milliliter/1.73m2).
8. Liver function tests (i.e., alanine aminotransferase, Aspartate Amino Transferase, alkaline phosphatase) greater than twice the upper limit of normal upon repeated measurements.
9. Diseases interfering with metabolism and/or ingestive behavior (e.g., myxedema, Cushing's disease, schizophrenia, major psychoses, unmanaged depression).
10. Use of drugs approved for the treatment of obesity.
11. Any clinically significant abnormality following the Investigator's review of the physical examination and clinical laboratory tests.
12. A baseline prolongation of ventricular activation and recovery interval after repeated measurements of \>450 millisecond; a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS).
13. Participation in an investigational drug trial within three months prior to dosing in the present study.

Primary outcomes:
measure: To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by the collection of Adverse Events.
timeFrame: For all study duration (approximately two months).
measure: To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by the collection of pre and post dose pharmacokinetics samples.
timeFrame: Before and after dose administration on Days 0 and 1.
measure: To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by the collection of vital signs.
timeFrame: On screening visit and on days 1 and 7.
measure: To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by the collection of Lab samples.
timeFrame: On screening visit and on days 1 and 7.
measure: To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by the collection of anthropometric measurement's.
timeFrame: On screening visit and on days 1 and 7. (height will be collected only in the screening visit).
measure: To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by an electrocardiogram examination.
timeFrame: On screening visit and on days 0,1 and 7.
measure: To determine the safety of a single subcutaneously administered dose of MD-18 in healthy subjects, as assessed by physical examination.
timeFrame: On screening visit and on days 1 and 7.
Secondary outcomes:
measure: Analysis of pharmacokinetics samples of MD-18 by lab methods.
timeFrame: Before and after dose administration on Days 0 and 1.
Other outcomes:
measure: Treatment-emergent Adverse Events (TEAEs) will be assessed.
timeFrame: For all study duration ( approximately two months).
measure: Tolerability (referred to as the dose-limiting tolerability) will be assessed by the number of reported cases with nausea and injection site reaction.
timeFrame: On days 0-3.
measure: Adverse events of special interest will be assessed.
timeFrame: For all study duration ( approximately two months).
Locations:
city: Ramat-gan
country: Israel
facility: Sheba Medical Center
state: Please select
Study officials:
affiliation: Cohen Global, Ltd.
name: Amir Tirosh, Prof
role: STUDY_CHAIR
References: