Relative Bioavailability and Food Effect Study of IX-01 Capsules in Healthy Men

• Sponsor: Ixchelsis Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02139826
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 3
• Duration (Months): 1
• Patients Per Site Per Month: 11.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Participants	Drug: IX-01	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: May 1, 2014
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IX-01 Capsule while Fasting Singe oral dose of 800 milligrams of IX-01 as a capsule, while fasting, in 1 of 3 treatment periods	Drug: IX-01
Experimental: IX-01 Aqueous Dispersion while Fasting Single oral dose of 800 milligrams IX-01 as an aqueous dispersion, while fasting in 1 of 3 treatment periods	Drug: IX-01
Experimental: IX-01 Capsule after Food Single oral dose of 800 milligrams IX-01 as a capsule, after food, in 1 of 3 treatment periods	Drug: IX-01

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. Peak Plasma Concentration (Cmax) of IX-01 [Pre-dose and up to 96 hours post dose]

7. Time to Peak Plasma Concentration (Tmax) of IX-01 [Pre-dose up to 96 hours post dose]

8. Elimination Half Life (t1/2) of IX-01 [Pre-dose up to 96 hours post dose]

9. Elimination Rate Constant (Kel) of IX-01 [Pre-dose up to 96 hours post last dose]

10. 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]

11. 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

Secondary Outcome Measures

1. Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs [Baseline to study completion (approximately 6 weeks)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hammersmith Medicines Research	London		United Kingdom

Sponsors and Collaborators

• Ixchelsis Limited

Investigators

• Study Director: Email: [e-mail], Ixchelsis Limited

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ixchelsis Limited
• ClinicalTrials.gov Identifier: NCT02139826
• Other Study ID Numbers: IX-0102
• First Posted: May 15, 2014
• Last Update Posted: Aug 20, 2020
• Last Verified: Aug 1, 2020

Study Results

Participant Flow

Pre-assignment Detail	One participant withdrew between arms following a non-serious adverse event - unlikely to be treatment-related

Arm/Group Title	Overall Study
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as an aqueous dispersion while fasting, or as a capsule while fasting, or as capsule while fed, in each of 3 treatment periods IX-01
Period Title: Overall Study
STARTED	12
COMPLETED	11
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	All 12 randomized participants
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.5 (9.22)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	12 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	12 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 8.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	10 83.3%
More than one race	1 8.3%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	12 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Capsule While Fasting
Arm/Group Description	Singe oral dose of 800 milligrams of IX-01 as a capsule, while fasting, in 1 of 3 treatment periods IX-01
Measure Participants	11
Geometric Mean (90% Confidence Interval) [Ratio: capsule fasted/acqueous fasted]	99.93

2. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Capsule After Food
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as a capsule, after food, in 1 of 3 treatment periods IX-01
Measure Participants	11
Geometric Mean (90% Confidence Interval) [Ratio: capsule fed/fasted]	148.85

3. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Capsule While Fasting
Arm/Group Description	Singe oral dose of 800 milligrams of IX-01 as a capsule, while fasting, in 1 of 3 treatment periods IX-01
Measure Participants	11
Geometric Mean (90% Confidence Interval) [Ratio: capsule/aqueous]	123.78

4. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Capsule After Food
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as a capsule, after food, in 1 of 3 treatment periods IX-01
Measure Participants	11
Geometric Mean (90% Confidence Interval) [Ratio: capsule fed/fasting]	175.46

5. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Aqueous Dispersion While Fasting	IX-01 Capsule While Fasting	IX-01 Capsule After Food
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as an aqueous dispersion, while fasting in 1 of 3 treatment periods IX-01	Singe oral dose of 800 milligrams of IX-01 as a capsule, while fasting, in 1 of 3 treatment periods IX-01	Single oral dose of 800 milligrams IX-01 as a capsule, after food, in 1 of 3 treatment periods IX-01
Measure Participants	11	11	12
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	20465 (38.9)	20522 (31.7)	31613 (27.3)

6. Primary Outcome

Title	Peak Plasma Concentration (Cmax) of IX-01
Time Frame	Pre-dose and up to 96 hours post dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Aqueous Dispersion While Fasting	IX-01 Capsule While Fasting	IX-01 Capsule After Food
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as an aqueous dispersion, while fasting in 1 of 3 treatment periods IX-01	Singe oral dose of 800 milligrams of IX-01 as a capsule, while fasting, in 1 of 3 treatment periods IX-01	Single oral dose of 800 milligrams IX-01 as a capsule, after food, in 1 of 3 treatment periods IX-01
Measure Participants	11	11	12
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1147 (39.9)	1428 (47.9)	2518.5 (22.7)

7. Primary Outcome

Title	Time to Peak Plasma Concentration (Tmax) of IX-01
Time Frame	Pre-dose up to 96 hours post dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Aqueous Dispersion While Fasting	IX-01 Capsule While Fasting	IX-01 Capsule After Food
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as an aqueous dispersion, while fasting in 1 of 3 treatment periods IX-01	Singe oral dose of 800 milligrams of IX-01 as a capsule, while fasting, in 1 of 3 treatment periods IX-01	Single oral dose of 800 milligrams IX-01 as a capsule, after food, in 1 of 3 treatment periods IX-01
Measure Participants	11	11	12
Median (Full Range) [hours]	1	1.5	4

8. Primary Outcome

Title	Elimination Half Life (t1/2) of IX-01
Time Frame	Pre-dose up to 96 hours post dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Aqueous Dispersion While Fasting	IX-01 Capsule While Fasting	IX-01 Capsule After Food
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as an aqueous dispersion, while fasting in 1 of 3 treatment periods IX-01	Singe oral dose of 800 milligrams of IX-01 as a capsule, while fasting, in 1 of 3 treatment periods IX-01	Single oral dose of 800 milligrams IX-01 as a capsule, after food, in 1 of 3 treatment periods IX-01
Measure Participants	11	11	12
Geometric Mean (Geometric Coefficient of Variation) [hours]	15 (60.7)	12.6 (32)	12.2 (40.2)

9. Primary Outcome

Title	Elimination Rate Constant (Kel) of IX-01
Time Frame	Pre-dose up to 96 hours post last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Aqueous Dispersion While Fasting	IX-01 Capsule While Fasting	IX-01 Capsule After Food
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as an aqueous dispersion, while fasting in 1 of 3 treatment periods IX-01	Singe oral dose of 800 milligrams of IX-01 as a capsule, while fasting, in 1 of 3 treatment periods IX-01	Single oral dose of 800 milligrams IX-01 as a capsule, after food, in 1 of 3 treatment periods IX-01
Measure Participants	11	11	12
Geometric Mean (Geometric Coefficient of Variation) [1/h]	0.046 (60.7)	0.055 (32)	0.057 (40.2)

10. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Aqueous Dispersion While Fasting	IX-01 Capsule While Fasting	IX-01 Capsule After Food
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as an aqueous dispersion, while fasting in 1 of 3 treatment periods IX-01	Singe oral dose of 800 milligrams of IX-01 as a capsule, while fasting, in 1 of 3 treatment periods IX-01	Single oral dose of 800 milligrams IX-01 as a capsule, after food, in 1 of 3 treatment periods IX-01
Measure Participants	11	11	12
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	19529 (34.5)	20218 (31.1)	31270 (26.7)

11. Primary Outcome

Title	Concentration of IX-01 in Cerebrospinal Fluid (CSF) After a Single Dose of the Liquid Formulation of IX-01
Description	Listed by time point of 1, 2, 4, 6 hours post dose
Time Frame	1, 2, 4 and 6 hours after dosing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Aqueous Dispersion While Fasting
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as an aqueous dispersion, while fasting in 1 of 3 treatment periods IX-01
Measure Participants	10
At 1 hour, 1 participant analyzed	27.8 (0)
At 2 hours, 2 participants analyzed	24.4 (2.97)
At 4 hours, 3 participants analyzed	54 (17.67)
At 6 hours, 4 participants analyzed	40 (21.04)

12. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IX-01 Aqueous Dispersion While Fasting	IX-01 Capsule While Fasting	IX-01 Capsule After Food
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as an aqueous dispersion, while fasting in 1 of 3 treatment periods IX-01	Singe oral dose of 800 milligrams of IX-01 as a capsule, while fasting, in 1 of 3 treatment periods IX-01	Single oral dose of 800 milligrams IX-01 as a capsule, after food, in 1 of 3 treatment periods IX-01
Measure Participants	11	11	12
Number [participants]	1 8.3%	1 NaN	2 NaN

Adverse Events

Time Frame	Up to 6 weeks
Adverse Event Reporting Description	The onset date/time of one non-serious event (toothache) was not recorded, so the treatment arm was unknown and not shown below, otherwise all events that occurred during the study period are shown including those that were unrelated
Arm/Group Title	IX-01 Aqueous Dispersion While Fasting		IX-01 Capsule While Fasting		IX-01 Capsule After Food
Arm/Group Description	Single oral dose of 800 milligrams IX-01 as an aqueous dispersion, while fasting in 1 of 3 treatment periods IX-01		Singe oral dose of 800 milligrams of IX-01 as a capsule, while fasting, in 1 of 3 treatment periods IX-01		Single oral dose of 800 milligrams IX-01 as a capsule, after food, in 1 of 3 treatment periods IX-01
All Cause Mortality
	IX-01 Aqueous Dispersion While Fasting		IX-01 Capsule While Fasting		IX-01 Capsule After Food
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	IX-01 Aqueous Dispersion While Fasting		IX-01 Capsule While Fasting		IX-01 Capsule After Food
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	IX-01 Aqueous Dispersion While Fasting		IX-01 Capsule While Fasting		IX-01 Capsule After Food
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/11 (72.7%)		3/11 (27.3%)		4/12 (33.3%)
Cardiac disorders
Atrioventricular block second degree	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Gastrointestinal disorders
Nausea	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0
Toothache	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Infections and infestations
Nasopharyngitis	1/11 (9.1%)	1	0/11 (0%)	0	1/12 (8.3%)	1
Rhinitis	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Injury, poisoning and procedural complications
Procedural Headache	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	4/11 (36.4%)	4	0/11 (0%)	0	1/12 (8.3%)	1
Myalgia	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Nervous system disorders
Headache	2/11 (18.2%)	2	2/11 (18.2%)	3	1/12 (8.3%)	1
Presyncope	2/11 (18.2%)	2	0/11 (0%)	0	0/12 (0%)	0
Dizziness	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0
Somnolence	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0
Head discomfort	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor may choose to collaborate on authorship, and sponsor's agent has 60-day review