PK study design
In this single centre, open-label cross-over study (EudraCT 2015-001818-99) volunteers received oral MR309 at doses of 400 mg QD for 10 days and 200 mg BID (12 h intervals) for 10 days, with a washout period of ≥10 days between the two dosing schedules. Allocation to dosing regimen sequence (QD–BID or BID–QD) was randomised using an automated random numbers scheme. MR309 was taken following an overnight fast for the morning doses on Days 1 and 10; at other time points participants fasted for 2 hr before and after dosing. Individuals included in this study were 18–45 years old with a body weight and body mass index (BMI) of 55–100 kg and 18.5–30 kg/m2, respectively. All participants were considered healthy based on their medical history (no significant illness during the 4 weeks prior to study entry), physical examination, laboratory parameters and electrocardiogram (ECG) tests. All participants agreed to use an effective method of contraception throughout the study duration, and pregnant and breastfeeding women were excluded. Other key exclusion criteria included a history of drug or alcohol abuse, use of opioid or opioid antagonist medication ≤30 days prior to study start, participation in a clinical trial ≤90 days prior to study start, and a history of frequent nausea or vomiting of any aetiology.