Schizophrenia
Conditions
Keywords
modified release formulation, pharmacokinetics
Brief summary
The aim of the study is to assess how MIN-101 is taken up by the body when given in different amounts and in different formulations. The drug will be given as a single dose in Part 1 of the study and during Part 2 of the study as multiple dose, once daily for 7 days. The ultimate aim is to find an optimal formulation which can be developed as a once daily dose for the treatment of schizophrenia.
Interventions
DRUGMIN-101
DRUGPlacebo
Sponsors
Minerva Neurosciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males (Part 1 and Part 2) or non-pregnant, non-lactating healthy females (Part 2 only) * Body mass index (BMI) of 18.0 to 30.0 kg/m2 * Must be CYP2D6 Extensive metabolizer * Must be willing and able to communicate and participate in the whole study * Must provide written informed consent * Must agree to use an adequate method of contraception Key
Exclusion criteria
* Subjects who have QTc \> 430 in male, \> 450 in female confirmed by a repeat ECG * Any family history of sudden cardiac death and Torsade de Points * No personal or family history of unexplained presyncope, syncope or orthostatic hypotension * History of any drug or alcohol abuse in the past 2 years * History or evidence of any medically diagnosed clinically significant psychiatric disorders * Suicidal tendencies or history of suicidal attempts * Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) * Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening * Females of childbearing potential who are pregnant or lactating (female subjects must have a negative urine pregnancy test at admission) * Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator * Positive drugs of abuse test result * Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 2 - Pharmacokinetic profile of MIN-101 and its main metabolites - Absolute QT intervals and QT intervals corrected using Fridericia formula (QTcF) | predose to Day 8 |
| Part 1 Pharmacokinetic profile of MIN-101 and its main metabolites (AUC (0-last), Tmax, Cmax, AUC (0-inf), %AUCextrap, Lambda z, T1/2 and parent:metabolites ratio | predose and 0.5h, 1h, 1.5h, 2h, 2.5h, 3H, 4H, 6h, 8h, 10h, 12h, 14h, 16h, 20h, 24h, 48h and 72h post-dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 Pharmacokinetic profile of MIN-101 in fed and fasted state | from predose up to 72 h post dosing | — |
| Part 2 Change from baseline in ECG parameters other than QT/QTc | from predose up to Day 8 | QTcB, QRS, RR, PR intervals, U waves, T waves morphology |
| Part 2 Change from baseline in heart rate and blood pressure | from predose up to Day 8 | — |
| Part 2 Incidence of QTc values greater than 450, 480 and 500 ms post dose | from predose up to Day 8 | — |
| Part 2 Safety and tolerability of MIN-101 (adverse events occurrence, physical examination, safety laboratory tests) | from predose up to Day 8 | — |
| Part 2 Incidence of QT/QTc changes from baseline greater than 30 and 60 ms post dose | from predose up to Day 8 | — |
| Part 1 Safety and tolerability (incidence of adverse events, safety laboratory, 12-lead ECGs, vital signs, physical examination) - | from predose up to 72 h post dosing | — |
Other
| Measure | Time frame |
|---|---|
| Changes in sleep architecture and sleep continuity | Day 6 |
Countries
United Kingdom
Outcome results
None listed