Healthy Participants
Conditions
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.
Interventions
DRUGIX-01
Sponsors
Ixchelsis Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of IX-01 in Cerebrospinal Fluid (CSF) After a Single Dose of the Liquid Formulation of IX-01 | 1, 2, 4 and 6 hours after dosing | Listed by time point of 1, 2, 4, 6 hours post dose |
| 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 | Pre-dose up to 96 hours post dose | — |
| 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 | Pre-dose up to 96 hours post dose | — |
| 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 | Pre-dose up to 96 hours post dose | — |
| 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 | Pre-dose up to 96 hours post dose | — |
| Area Under the Plasma Concentration Time Curve From Time 0 to Infinity, Following a Single Dose of IX-01 | Pre-dose and up to 96 hours post dose | — |
| Peak Plasma Concentration (Cmax) of IX-01 | Pre-dose and up to 96 hours post dose | — |
| Time to Peak Plasma Concentration (Tmax) of IX-01 | Pre-dose up to 96 hours post dose | — |
| Elimination Half Life (t1/2) of IX-01 | Pre-dose up to 96 hours post dose | — |
| Elimination Rate Constant (Kel) of IX-01 | Pre-dose up to 96 hours post last dose | — |
| Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Measurable Sample of IX-01 | Pre-dose to the time of the last measurable sample | — |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs | Baseline to study completion (approximately 6 weeks) |
Countries
United Kingdom
Participant flow
Pre-assignment details
One participant withdrew between arms following a non-serious adverse event - unlikely to be treatment-related
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All 12 randomized participants | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 32.5 years STANDARD_DEVIATION 9.22 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United Kingdom | 12 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 11 | 3 / 11 | 4 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 12 |
Outcome results
Primary
Area Under the Plasma Concentration Time Curve From Time 0 to Infinity, Following a Single Dose of IX-01
Time frame: Pre-dose and up to 96 hours post dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IX-01 Capsule While Fasting | Area Under the Plasma Concentration Time Curve From Time 0 to Infinity, Following a Single Dose of IX-01 | 20465 h*ng/mL | Geometric Coefficient of Variation 38.9 |
| IX-01 Capsule While Fasting | Area Under the Plasma Concentration Time Curve From Time 0 to Infinity, Following a Single Dose of IX-01 | 20522 h*ng/mL | Geometric Coefficient of Variation 31.7 |
| IX-01 Capsule After Food | Area Under the Plasma Concentration Time Curve From Time 0 to Infinity, Following a Single Dose of IX-01 | 31613 h*ng/mL | Geometric Coefficient of Variation 27.3 |
Primary
Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Measurable Sample of IX-01
Time frame: Pre-dose to the time of the last measurable sample
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IX-01 Capsule While Fasting | Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Measurable Sample of IX-01 | 19529 h*ng/mL | Geometric Coefficient of Variation 34.5 |
| IX-01 Capsule While Fasting | Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Measurable Sample of IX-01 | 20218 h*ng/mL | Geometric Coefficient of Variation 31.1 |
| IX-01 Capsule After Food | Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Measurable Sample of IX-01 | 31270 h*ng/mL | Geometric Coefficient of Variation 26.7 |
Primary
Concentration of IX-01 in Cerebrospinal Fluid (CSF) After a Single Dose of the Liquid Formulation of IX-01
Listed by time point of 1, 2, 4, 6 hours post dose
Time frame: 1, 2, 4 and 6 hours after dosing
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IX-01 Capsule While Fasting | Concentration of IX-01 in Cerebrospinal Fluid (CSF) After a Single Dose of the Liquid Formulation of IX-01 | At 1 hour, 1 participant analyzed | 27.8 ng/mL | Standard Deviation 0 |
| IX-01 Capsule While Fasting | Concentration of IX-01 in Cerebrospinal Fluid (CSF) After a Single Dose of the Liquid Formulation of IX-01 | At 2 hours, 2 participants analyzed | 24.4 ng/mL | Standard Deviation 2.97 |
| IX-01 Capsule While Fasting | Concentration of IX-01 in Cerebrospinal Fluid (CSF) After a Single Dose of the Liquid Formulation of IX-01 | At 4 hours, 3 participants analyzed | 54 ng/mL | Standard Deviation 17.67 |
| IX-01 Capsule While Fasting | Concentration of IX-01 in Cerebrospinal Fluid (CSF) After a Single Dose of the Liquid Formulation of IX-01 | At 6 hours, 4 participants analyzed | 40 ng/mL | Standard Deviation 21.04 |
Primary
Elimination Half Life (t1/2) of IX-01
Time frame: Pre-dose up to 96 hours post dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IX-01 Capsule While Fasting | Elimination Half Life (t1/2) of IX-01 | 15 hours | Geometric Coefficient of Variation 60.7 |
| IX-01 Capsule While Fasting | Elimination Half Life (t1/2) of IX-01 | 12.6 hours | Geometric Coefficient of Variation 32 |
| IX-01 Capsule After Food | Elimination Half Life (t1/2) of IX-01 | 12.2 hours | Geometric Coefficient of Variation 40.2 |
Primary
Elimination Rate Constant (Kel) of IX-01
Time frame: Pre-dose up to 96 hours post last dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IX-01 Capsule While Fasting | Elimination Rate Constant (Kel) of IX-01 | 0.046 1/h | Geometric Coefficient of Variation 60.7 |
| IX-01 Capsule While Fasting | Elimination Rate Constant (Kel) of IX-01 | 0.055 1/h | Geometric Coefficient of Variation 32 |
| IX-01 Capsule After Food | Elimination Rate Constant (Kel) of IX-01 | 0.057 1/h | Geometric Coefficient of Variation 40.2 |
Primary
Peak Plasma Concentration (Cmax) of IX-01
Time frame: Pre-dose and up to 96 hours post dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IX-01 Capsule While Fasting | Peak Plasma Concentration (Cmax) of IX-01 | 1147 ng/mL | Geometric Coefficient of Variation 39.9 |
| IX-01 Capsule While Fasting | Peak Plasma Concentration (Cmax) of IX-01 | 1428 ng/mL | Geometric Coefficient of Variation 47.9 |
| IX-01 Capsule After Food | Peak Plasma Concentration (Cmax) of IX-01 | 2518.5 ng/mL | Geometric Coefficient of Variation 22.7 |
Primary
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
Time frame: Pre-dose up to 96 hours post dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| IX-01 Capsule While Fasting | 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 | 99.93 Ratio: capsule fasted/acqueous fasted |
Primary
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
Time frame: Pre-dose up to 96 hours post dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| IX-01 Capsule While Fasting | 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 | 123.78 Ratio: capsule/aqueous |
Primary
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
Time frame: Pre-dose up to 96 hours post dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| IX-01 Capsule While Fasting | 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 | 175.46 Ratio: capsule fed/fasting |
Primary
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
Time frame: Pre-dose up to 96 hours post dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| IX-01 Capsule While Fasting | 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 | 148.85 Ratio: capsule fed/fasted |
Primary
Time to Peak Plasma Concentration (Tmax) of IX-01
Time frame: Pre-dose up to 96 hours post dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IX-01 Capsule While Fasting | Time to Peak Plasma Concentration (Tmax) of IX-01 | 1 hours |
| IX-01 Capsule While Fasting | Time to Peak Plasma Concentration (Tmax) of IX-01 | 1.5 hours |
| IX-01 Capsule After Food | Time to Peak Plasma Concentration (Tmax) of IX-01 | 4 hours |
Secondary
Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs
Time frame: Baseline to study completion (approximately 6 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IX-01 Capsule While Fasting | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs | 1 participants |
| IX-01 Capsule While Fasting | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs | 1 participants |
| IX-01 Capsule After Food | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs | 2 participants |