Clinical trial NCT02139826: Relative Bioavailability and Food Effect Study of IX-01 Capsules in Healthy Men
Official title: A Randomised, Single-dose, 3-way Crossover Study to Evaluate the Relative Bioavailability of the IX-01 Capsule Formulation Compared With the IX-01 Aqueous Dispersion Formulation, and the Effect of Food on the IX-01 Capsule Formulation, in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Lead sponsor: Ixchelsis Limited
Sponsor class: INDUSTRY
First posted: 2014-05-15
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the absorption and blood levels of IX-01 when given as a capsule compared to liquid form, and how food affects the absorption in healthy men.


Eligibility criteria: Inclusion Criteria:

* A body mass index (Quetelet index) in the range 18-30 kilograms/meters squared (kg/m2)
* Body Mass Index = weight \[kg\] divided by (height \[m\])2
* Total body weight greater than (\>)50 kg at screening
* Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial
* Participants and their partners must be willing to use adequate forms of contraception and to comply with the contraception requirements during the trial and for 4 months after the last dose of medication
* Willingness to give written consent to have data entered into The Over Volunteering Prevention System

Exclusion Criteria:

* Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment, including:

  * Lipid and/or liver function test results \>1.25 x Upper Limit of Normal (ULN) or other clinical laboratory blood biochemistry test results outside the normal reference range unless discussed and approved by sponsor
  * International normalised ratio (INR) of \>1.2 or a platelet count \< 150 x 109/Liter
  * History of unexplained syncope
  * Family history of unexplained sudden death, or sudden death due to long QT syndrome
  * Fridericia Correction Formula (QTcF) interval \>450 milliseconds (msec) at screening
  * Bundle branch block and other conduction abnormalities, other than mild first degree atrio-ventricular block
  * Irregular rhythms other than sinus arrhythmia or occasional supraventricular ectopic beats
  * T-wave configuration of insufficient quality for determination of QT interval, as assessed by the investigator
* Presence of acute or chronic illness or history of chronic illness sufficient to invalidate participation in the trial
* Impaired gastrointestinal, endocrine, thyroid, hepatic, cardiovascular, respiratory, haematological, renal or neurological function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness
* Surgery (for example (e.g.) stomach bypass) or medical condition that might affect absorption, metabolism or elimination of medicines
* Any skin condition, abnormality of the lumbar spine, medical or surgical condition that would preclude lumbar puncture (e.g. coagulopathy, local or systemic infection, left ventricular outflow obstruction, aortic stenosis, previous back surgery)
* Presence or history of severe adverse reaction to any drug
* Use of any prescription or over-the-counter medicine during the 14 days before the first dose of trial medication, or intention to use any medicine during the trial, with the exception of short courses of medication considered by the investigator not to interfere with the safety of the participant or the integrity of the trial data (such as acetaminophen (paracetamol))
* Current use of any herbal remedy or nutritional supplement, or intention to use any such product during the study
* Participation in another clinical trial of a new chemical entity or a prescription medicine within the previous 3 months.
* Previous participation in this trial or any other clinical trial of an oxytocin receptor antagonist
* Presence or history of drug or alcohol abuse, or intake of more than 21 units of alcohol weekly or more than 5 cigarettes daily
* Blood pressure and heart rate in supine position at the screening examination outside the ranges 100-130 millimeters of mercury (mm Hg) systolic, 60-90 mm Hg diastolic; heart rate 50-100 beats/minute. Measurements must be made in duplicate, and all values must fall within the acceptable ranges
* Possibility that the participant will not cooperate with the requirements of the protocol
* Evidence of drug abuse on urine testing
* Positive test for hepatitis B, hepatitis C, Human Immunodeficiency Virus 1 (HIV1) or Human Immunodeficiency Virus 2 (HIV2)
* Loss of more than 400 mL blood during the 3 months before the trial, e.g. as a blood donor
* Objection by General Practitioner (GP), on medical grounds, to participant entering trial
* Employee of the investigator site or any company involved in sponsoring, organizing or conducting the trial, or immediate family of the employee

Primary outcomes:
measure: Relative Bioavailability (Frel) of a Capsule Compared to a Liquid Formulation of IX-01 While Fasting, as Calculated by a Ratio of Area Under the Plasma Concentration Time Curve From Time 0 to Infinity
timeFrame: Pre-dose up to 96 hours post dose
measure: Relative Bioavailability (Frel) of a Capsule Formulation of IX-01 in the Fed State Compared to the Fasted State, as Calculated by a Ratio of Area Under the Plasma Concentration Time Curve From Time 0 to Infinity
timeFrame: Pre-dose up to 96 hours post dose
measure: Relative Bioavailability (Frel) of a Capsule Compared With a Liquid Formulation of IX-01 While Fasting, as Calculated by a Ratio of Peak Plasma Concentrations
timeFrame: Pre-dose up to 96 hours post dose
measure: Relative Bioavailability (Frel) of a Capsule Formulation of IX-01 in a Fed State Compared to a Fasted State, as Calculated by a Ratio of Peak Plasma Concentrations
timeFrame: Pre-dose up to 96 hours post dose
measure: Area Under the Plasma Concentration Time Curve From Time 0 to Infinity, Following a Single Dose of IX-01
timeFrame: Pre-dose and up to 96 hours post dose
measure: Peak Plasma Concentration (Cmax) of IX-01
timeFrame: Pre-dose and up to 96 hours post dose
measure: Time to Peak Plasma Concentration (Tmax) of IX-01
timeFrame: Pre-dose up to 96 hours post dose
measure: Elimination Half Life (t1/2) of IX-01
timeFrame: Pre-dose up to 96 hours post dose
measure: Elimination Rate Constant (Kel) of IX-01
timeFrame: Pre-dose up to 96 hours post last dose
measure: Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Measurable Sample of IX-01
timeFrame: Pre-dose to the time of the last measurable sample
measure: Concentration of IX-01 in Cerebrospinal Fluid (CSF) After a Single Dose of the Liquid Formulation of IX-01
timeFrame: 1, 2, 4 and 6 hours after dosing
Secondary outcomes:
measure: Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs
timeFrame: Baseline to study completion (approximately 6 weeks)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Hammersmith Medicines Research
Study officials:
affiliation: Ixchelsis Limited
name: Email: Ixchelsis@Choruspharma.com
role: STUDY_DIRECTOR
References: