A Phase 1, Randomised, Double-blind, Placebo-controlled, First in Human Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of MVD1 in Normal Weight or Overweight Healthy Adult Volunteers and Multiple Doses of MVD1 in Overweight or Obese Healthy Adult Volunteers

Inclusion Criteria46

• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
• Male or female, 18-60 years of age inclusive at the time of screening.
• Body mass index (BMI) = 20 and < 30 kg/m2 at the time of screening.
• Female participants:
• a. Must be of non-childbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy or bilateral tube ligation/occlusion at least 6 weeks before the Screening visit) or postmenopausal where menopause is defined as 12 months of amenorrhea without an alternative medical cause (females must have a documented serum follicle stimulating hormone level consistent with postmenopausal status, per local laboratory guidelines) OR
• b. If of childbearing potential (defined as any female who has experienced menarche and who has not undergone surgical sterilisation and is not postmenopausal), must agree not to attempt to become pregnant, must not donate ova and must agree to use an acceptable form of contraception from signing the consent form until at least 30 days after the last dose of study drug.
• Male participants:
• a. Must be biologically or surgically sterile (i.e, have had a vasectomy at least 3 months prior to screening) OR
• b. If not biologically or surgically sterile, must agree not to donate sperm and must agree to use an acceptable contraceptive method in addition to having the female partner use an acceptable contraceptive method from signing the consent form until at least 90 days after the last dose of study drug.
• Willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.
• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
• Male or female, 25-60 years of age inclusive at the time of screening.
• In good health as determined by the outcome of medical history, physical examination, and clinical judgement by the Investigator. Chronic stable non-inflammatory conditions such as abnormal fasting glycemia, hypertension, hyperlipidemia, osteoarthritis, gout, Chronic Pain Disorders, Thyroid Disease, controlled psychiatric conditions such as anxiety or depression, are permitted, as determined by the Investigator.
• Body mass index (BMI) between 28 and 35 kg/m2 inclusive at the time of screening.
• Female participants:
• a. Must be of non-childbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy or bilateral tube ligation/occlusion at least 6 weeks before the Screening visit) or postmenopausal where menopause is defined as 12 months of amenorrhea without an alternative medical cause (females must have a documented serum follicle stimulating hormone level consistent with postmenopausal status, per local laboratory guidelines) OR
• b. If of childbearing potential (defined as any female who has experienced menarche and who has not undergone surgical sterilisation and is not postmenopausal), must agree not to attempt to become pregnant, must not donate ova and must agree to use an acceptable form of contraception from signing the consent form until at least 30 days after the last dose of study drug.
• Male participants:
• a. Must be biologically or surgically sterile (i.e, have had a vasectomy at least 3 months prior to screening) OR
• b. If not biologically or surgically sterile, must agree not to donate sperm and must agree to use an acceptable contraceptive method in addition to having the female partner use an acceptable contraceptive method from signing the consent form until at least 90 days after the last dose of study drug.
• Willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.
• Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications
• Any history of malignant disease in the last 10 years (excludes surgically resected skin and in situ cervical squamous cell or basal cell carcinoma)
• Screening 12-lead ECG outside the normal range for the triplicate mean (QTcF males > 450 msec; females > 470 msec) or with abnormalities, which are hazardous to the participant according to the opinion of the Investigator
• Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia
• Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration
• History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrhythmia
• Change in body weight of = 5 % within 6 months prior to screening visit
• Liver function test results elevated more than 1.5-fold above the ULN for GGT, bilirubin (total or unconjugated), ALP, AST or ALT
• Positive test results for active HIV, HBsAg or HCV antibodies at the screening visit
• Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
• Estimated glomerular filtration rate (eGFR) < 60 mL/min /1.73 m2 or serum creatinine more than 1.5-fold above the ULN
• History of substance abuse or alcohol abuse (defined as regularly consume more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]) within 12 weeks prior to the screening visit
• Positive urine cotinine, drugs of abuse or alcohol breath test results at the screening visit or at check-in (Day -1).
• Use of any prescription or over-the-counter medication (including herbal products, diet aids, hormone supplements, topical ointments, vitamins and dietary supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, with the exception of hormonal contraceptives, medications used to manage AEs including the occasional use of paracetamol (doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3 consecutive days), stable use (4 weeks or longer prior to screening) of medications used to treat hypertension and high cholesterol and medications for hay fever.
• Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer’s ability to participate in the trial
• Known hypersensitivity to any of the study drug ingredients.
• Use of any vaccinations within 14 days prior to the first study drug administration
• For women of childbearing potential, a positive serum pregnancy test at the screening visit or a positive urine pregnancy test (with confirmatory serum pregnancy test) at check-in (Day -1)
• Females who are lactating at any time during the study
• Donation of blood or plasma within 30 days prior to first study drug administration, or loss of whole blood of more than 500 mL within 30 days prior to first study drug administration, or receipt of a blood transfusion within 1 year of first study drug administration
• Participation in another clinical trial of an investigational drug within 60 days or 5 half-lives of the investigational agent (whichever is longer) prior to the first study drug administration
• Difficulty in swallowing the study medication
• Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements
• A screening urinalysis result, or first morning urine protein dipstick result on Day 1 prior to first dose of study drug showing more than a trace of protein. Test may be repeated to confirm.
• Body weight > 120 kg at screening