Pharmacokinetic Study of MIN-101 in Healthy Subjects

Schizophrenia Clinical Trial

Official title:

A Two-Part Study Designed to Evaluate the Pharmacokinetic Profile of MIN-101 and Its Main Metabolites Following Single and Multiple Dose Modified Release Prototype Formulation Administration in Healthy Cytochrome P450 2D6 Extensive Metabolizer Male and Female Subjects, and to Evaluate the Relationship Between the Pharmacokinetic Profile of MIN-101 and Its Main Metabolites and Cardiovascular Parameters.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02232529
• Other study ID #: MIN-101C02
• Secondary ID: 2014-001613-53
• Status: Completed
• Phase: Phase 1
• First received: September 3, 2014
• Last updated: February 23, 2015
• Start date: September 2014
• Est. completion date: February 2015

Study information

• Verified date: February 2015
• Source: Minerva Neurosciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• MIN-101

• Placebo

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical	Ruddington, Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Minerva Neurosciences

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in sleep architecture and sleep continuity		Day 6	No
Primary	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	No
Primary	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	No
Secondary	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	Yes
Secondary	Part 1 Pharmacokinetic profile of MIN-101 in fed and fasted state		from predose up to 72 h post dosing	No
Secondary	Part 2 Change from baseline in ECG parameters other than QT/QTc	QTcB, QRS, RR, PR intervals, U waves, T waves morphology	from predose up to Day 8	Yes
Secondary	Part 2 Change from baseline in heart rate and blood pressure		from predose up to Day 8	Yes
Secondary	Part 2 Incidence of QT/QTc changes from baseline greater than 30 and 60 ms post dose		from predose up to Day 8	Yes
Secondary	Part 2 Incidence of QTc values greater than 450, 480 and 500 ms post dose		from predose up to Day 8	Yes
Secondary	Part 2 Safety and tolerability of MIN-101 (adverse events occurrence, physical examination, safety laboratory tests)		from predose up to Day 8	Yes