Food Effect, Efficacy and Safety of MKP10241 in Healthy and Obese Adult Participants, With and Without Diabetes

Официальное название

A Phase 2a, Double-blind, Randomized, Placebo-controlled, Study to Assess Food Effect, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Oral Doses of MKP10241 in Healthy and Obese Adult Participants, With and Without Type 2 Diabetes Mellitus

Обзор

The goal of this intervention study is to evaluate the safety, tolerability and pharmacokinetics (PK) and pharmacodynamics (PD) of multiple doses of MKP10241 in obese participants with and without T2DM in 3 parts. The main parameters it aims to answers are : 1. Does food effects the pharmacokinetic parameters following a single dose of MKP10241 in healthy participants? 2. Will multiple ascending doses of MKP10241 in obese participants with or without T2DM characterize changes in the plasma pharmacokinetic profile and pharmacodynamic effects? 3. What treatment emergent adverse events or discontinuation is experienced following single and multiple ascending doses of MKP10241 in healthy and obese participants with or without T2DM? This study will be compared against a placebo which is matched in appearance to MKP10241 at dosage strengths. Participants will: 1. Part 1: Take MKP10241 400 mg or Placebo on Day 1 and Day 8. Part 2: Take MKP10241 200 mg, 300 mg and 400 mg or Placebo daily from Day 1 to Day 28 Part 3: Take MKP10241 300 mg and 400 mg or Placebo daily from Day 1 to Day 28 2. Visit the clinical research unit for dose administration, admission or follow up. 3. Will be monitored by the Safety Monitoring Committee.

Вмешательства

• Препарат MKP10241
  Oral liquid suspension of unit dose strength 6.6 mg/mL
• Препарат Placebo
  Oral liquid suspension matched in appearance to MKP10241 at dosage strengths

Первичные конечные точки

• Part 1 - Food effect of single dose of MKP10241 on Maximum concentration of drug (Cmax) [Срок оценки: 18 days]
• Part 1 - Food effect of single dose of MKP10241 on Apparent total clearance of drug (CL/F) [Срок оценки: 18 days]
• Part 1 - Food effect of single dose of MKP10241 on Time to maximum concentration (Tmax) [Срок оценки: 18 days]
• Part 1 - Food effect of single dose of MKP10241 on elimination half life (t1/2 ) [Срок оценки: 18 days]
• Part 1 - Food effect of single dose of MKP10241 on lag time (Tlag) [Срок оценки: 18 days]
• Part 1 - Food effect of single dose of MKP10241 on Apparent Volume of distribution of drug (V/F) [Срок оценки: 18 days]
• Part 1 - Food effect of single dose of MKP10241 on Area under the curve from time 0 to 24hrs - AUC (0-24h) [Срок оценки: 18 days]
• Part 1 - Food effect of single dose of MKP10241 on AUC(0-last) [Срок оценки: 18 days]
• Part 1 - Food effect of single dose of MKP10241 on AUC(0-inf) [Срок оценки: 18 days]
• Part 2 - To evaluate the incidence of treatment emergent adverse events and participant tolerance of MKP10241 following multiple doses in obese participants [Срок оценки: 35 days]

Вторичные конечные точки (12)

• Part 1 - To evaluate the incidence of treatment emergent adverse events and of MKP10241 following a single dose administered orally under fasting and fed conditions. [Срок оценки: 18 days]
• Part 2 - Pharmacokinetics and Pharmacodynamics of MKP10241 following multiple doses in obese adult participants [Срок оценки: Baseline to Day 28]
• Part 2 - Pharmacokinetics and Pharmacodynamics of MKP10241 following multiple doses in obese adult participants [Срок оценки: Baseline to Day 28]
• Part 2 - Pharmacokinetics and Pharmacodynamics of MKP10241 following multiple doses in obese adult participants [Срок оценки: Baseline to Day 28]
• Part 2 - Pharmacokinetics and Pharmacodynamics of MKP10241 following multiple doses in obese adult participants. [Срок оценки: Baseline to Day 28]
• Part 3 - Pharmacokinetic and Pharmacodynamic effects of MKP10241 following multiple doses administration in obese adult participants with T2DM. [Срок оценки: Baseline to Day 28]
• Part 3 - Pharmacokinetic and Pharmacodynamic effects of MKP10241 following multiple doses administration in obese adult participants with T2DM. [Срок оценки: Baseline to Day 28]
• Part 3 - Pharmacokinetic and Pharmacodynamic effects of MKP10241 following multiple doses administration in obese adult participants with T2DM. [Срок оценки: Baseline to Day 28]
• Part 3 - Pharmacokinetic and Pharmacodynamic effects of MKP10241 following multiple doses administration in obese adult participants with T2DM. [Срок оценки: Baseline to Day 28]
• Part 2 - Pharmacokinetics and Pharmacodynamics of MKP10241 following multiple doses in obese adult participants [Срок оценки: Baseline to Day 28]
• Part 2 - Pharmacokinetics and Pharmacodynamics of MKP10241 following multiple doses in obese adult participants [Срок оценки: From screening visit to day 29]
• Part 2 - Pharmacokinetics and Pharmacodynamics of MKP10241 following multiple doses in obese adult participants [Срок оценки: Day 1, 7, 14, 21 and 28]

Критерии участия

Критерии включения

• Male or female participants between 18 to 60 years of age
• Considered healthy by the Investigator. Part 1: BMI of 18 to 30 kg/m2, and weight being not less than 50 kg. Part 2/3: BMI of ≥32 kg/m2
• Part 1/2: Fasting plasma glucose (FPG) between 3.9 mmol/L and 6.1 mmol/L. Part 3: FPG greater than or equal to 6.94 mmol/L and less than or equal to 14.43 mmol/L
• A nonsmoker/social smoker, defined as not having smoked more than 5 cigarettes or equivalent per day in the 3 months prior to Screening.
• Able to abstain from the consumption of alcohol and any alcohol-containing products from 48 hours before dosing to the End of Study Visit.
• Female participants must be of nonchildbearing potential or, if of childbearing potential, must agree to use 1 form of highly effective contraceptive method, plus an additional barrier method of contraception between signing consent
• Male participants who are sexually active must use a condom from Screening until at least 90 days after the last dose of study intervention (or be surgically sterile. Female partners of childbearing potential must use a highly effective method of contraception.
• Capable of giving signed Informed Consent
• Willing and able to adhere to study restrictions and to be confined at the CRU.
• Part 3: Participants with an established diagnosis of type 2 diabetes mellitus
• Part 3: Participants; type 2 diabetes mellitus must be managed by diet and exercise alone or by stable dose of metformin (for ≥2 months); the use of other antidiabetic therapies is prohibited

Критерии исключения

• Clinically significant haematological findings at Screening.
• Hepatic impairment including aspartate aminotransferase (AST), alanine transaminase (ALT), or alkaline phosphatase ≥1.5 times upper limit of normal (ULN), total bilirubin ≥2.0 times ULN, albumin ≤3.0 g/L, serum amylase or lipase ≥1.5 times ULN at Screening.
• Renal impairment, such as creatinine ≥ULN, estimated glomerular filtration rate (eGFR) of ≤80 mL/minute/1.73m2 in adults, as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
• Positive polymerase chain reaction (PCR) test for severe-acute-respiratory-syndrome-related coronavirus (SARS-CoV-2)
• A history of non-febrile seizures.
• Positive pregnancy test result at Screening or on admission to the CRU,
• Any major surgery within 60 days prior to Screening, or planned major surgery during the study.
• Any history of malignant disease excluding surgically resected skin and in-situ cervical squamous cell or basal cell carcinoma.
• Suspected hypersensitivity to MKP10241 and any components of MKP10241 liquid suspension
• Any other condition which makes the participant unsuitable for study participation as judged by the Investigator or designee.
• Participant has any history or evidence of any clinically significant disease
• Prior or planned (during study period) bariatric surgery (e.g. gastric bands, gastroplasty Roux-e-Y gastric bypass) or ileal resection.
• Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-V) substance use disorders and alcohol abuse within 12 months prior to Screening and/or positive alcohol breath test at Screening or admission.
• Positive result for drugs of abuse at Screening or admission.
• Use of live attenuated vaccines within 14 days prior to dosing
• The use of medications (other than paracetamol), including hormonal contraceptives
• Receipt of any other investigational medicinal product within one month or five half-lives (whichever is longer) prior to dosing.
• Clinically significant ECG findings: QTcF value ≥450 ms for males or ≥470 ms for females at Screening or Day -1
• Participants with a mean systolic blood pressure >140 mmHg, mean diastolic blood pressure >90 mmHg at Screening.
• Positive blood screen for human immunodeficiency virus antibody (HIV), hepatitis B surface antigen (HBsAg), syphilis, hepatitis C virus (HCV).
• Change in body weight of ≥ 10% within 3 months prior to the Screening visit.
• Donation or blood collection of more than 1 unit (approximate 450 mL) of blood (or blood products, plasma) or acute loss of blood during the 30 days prior to Screening.
• Part 3: Type 1 diabetes mellitus, maturity-onset diabetes of the young, or other forms of diabetes.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Австралия · 1 центр

• Veritus Research — Bayswater

Идентификаторы

NCT: NCT07098663 · MKP10241-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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