Relative Bioavailability Study of IX-01 Caplet Versus Aqueous Dispersion and Food Effect of the Caplet in Healthy Males

NCT02962531 | Completed Phase 1

• 1 other identifier: IX-0106
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label, randomized, three-period, three-way crossover trial of single doses of IX-01 in 12 healthy male subjects. In each period, subjects will receive a single oral dose of 1600 mg IX-01, either as an aqueous dispersion in a fasted state, or as caplets in the fed or fasted state

Conditions

Healthy

Outcome Measures

Primary Outcomes (12)

• Pharmacokinetic parameter peak plasma concentration of IX-01 (C max)

  Relative bioavailability of the caplet formulation of IX-01compared with the aqueous dispersion formulation when administered in the fasted state

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Pharmacokinetic parameter time of peak plasma concentration of IX-01 (t max)

  Relative bioavailability of the caplet formulation of IX-01compared with the aqueous dispersion formulation when administered in the fasted state

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Pharmacokinetic parameter terminal half-life (t 1/2)

  Relative bioavailability of the caplet formulation of IX-01compared with the aqueous dispersion formulation when administered in the fasted state

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Pharmacokinetic parameter elimination rate constant (K el)

  Relative bioavailability of the caplet formulation of IX-01compared with the aqueous dispersion formulation when administered in the fasted state

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Relative bioavailability of the caplet formulation of IX-01 compared with the aqueous dispersion formulation (fasted)

  Relative bioavailability of the caplet formulation of IX-01compared with the aqueous dispersion formulation when administered in the fasted state

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Pharmacokinetic parameter area under the concentration-time curve (AUC 0-inf)

  Relative bioavailability of the caplet formulation of IX-01compared with the aqueous dispersion formulation when administered in the fasted state

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• area under the concentration-time curve from 0 up to the time of last quantifiable concentration (AUC last)

  Relative bioavailability of the caplet formulation of IX-01compared with the aqueous dispersion formulation when administered in the fasted state

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• The relative bioavailability of IX-01, as judged by AUC 0-inf (F rel)

  Relative bioavailability of the caplet formulation of IX-01 compared with the aqueous dispersion formulation when administered in the fasted state

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Comparison of Maximum Plasma Concentration [Cmax] in fed versus fasted states

  To determine the effect of a high-fat meal on the pharmacokinetic profile of the IX-01 caplet formulation

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Comparison of Area Under the Curve [AUC] in fed versus fasted states

  To determine the effect of a high-fat meal on the pharmacokinetic profile of the IX-01 caplet formulation

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Comparison of Time to Maximum Plasma Concentration [Tmax] in fed versus fasted states

  To determine the effect of a high-fat meal on the pharmacokinetic profile of the IX-01 caplet formulation

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Comparison of the Area Under the Curve [AUC] in fed versus fasted states

  To determine the effect of a high-fat meal on the pharmacokinetic profile of the IX-01 caplet formulation

  pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

Secondary Outcomes (1)

• Safety monitoring - adverse events, laboratory data, ECGs, vital signs

  Day 0 to Day 21

Study Arms (3)

Treatment A

EXPERIMENTAL

A single 1600 mg (4 x 400 caplets) oral dose of IX-01 under fasted conditions

Drug: IX-01 caplets 1600 mg (4 x 400 mg), fasted

Treatment B

EXPERIMENTAL

A single 1600 mg (4 x 400 caplets) oral dose of IX-01 under fed conditions

Drug: IX-01 caplets 1600 mg (4 x 400 mg), fed

Treatment C

EXPERIMENTAL

A single 1600 mg aqueous dispersion (20 mL) oral dose of IX-01 under fasted conditions.

Drug: IX-01 aqueous dispersion 1600 mg (20 mL), fasted

Interventions

IX-01 caplets 1600 mg (4 x 400 mg), fasted DRUG

oral dose under fasted conditions

Treatment A

IX-01 caplets 1600 mg (4 x 400 mg), fed DRUG

oral dose under fed conditions

Treatment B

IX-01 aqueous dispersion 1600 mg (20 mL), fasted DRUG

oral dose under fasted conditions

Treatment C

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index between 18 and 30 kg/m2
• Body weight of ˃60 kg (132 lbs) at screening
• Able to understand the nature of the trial and any hazards of participating. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of the entire trial
• Willing to comply with the contraception requirements of the trial
• Willing to give written consent to participate
• Willing and able to remain in the study unit for the entire duration of each confinement period and return for outpatient visits
• Willing and able to consume the entire high-calorie, high-fat breakfast meal in the designated timeframe required during fed study period
• Vital signs at both screening and at baseline within: heart rate: 50-90 beats per minute; systolic blood pressure: 100-130 mmHg; diastolic: 60-90 mmHg

You may not qualify if:

• Clinically relevant abnormal history, physical findings, ECG, or laboratory values at screening that could interfere with the objectives of the trial or safety of the volunteer, including any of the following:
• Lipid and/or liver function test results \>1.25 times upper limit of normal or another clinical laboratory result judged clinically significant
• An international normalised ratio of \>1.2 or a platelet count \<150 x10\^3/mL
• History of unexplained syncope
• Family history of unexplained sudden death or sudden death due to long QT syndrome
• QTcF interval \>450 msec at screening
• Bundle branch block or another conduction abnormality during an ECG, other than mild first degree atrio-ventricular block, judged clinically significant
• Irregular rhythms during an ECG, other than sinus arrhythmia or occasional supraventricular ectopic beats, judged clinically significant
• T-wave configuration of insufficient quality for determination of QT interval, as assessed by ECG and judged clinically significant by the Investigator
• Presence of acute or chronic illness or history of chronic illness sufficient to invalidate participation in the trial or make study participation unnecessarily hazardous
• Impaired gastrointestinal, endocrine, thyroid, hepatic, cardiovascular, respiratory, hematological, renal or neurological function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness
• Surgery (e.g. stomach bypass) or medical condition that might affect absorption, metabolism, or elimination of medicines
• Presence or history of severe adverse reaction to any drug and/or a history of skin reactions (rashes) to any drug
• Previous allergic response which involved hives, swelling, shortness of breath, or anaphylaxis
• Has used any over-the-counter medications, nutritional or dietary supplements, herbal preparations, or vitamins, except short courses of medication (such as acetaminophen), that could interfere with subject safety or the integrity of the trial data within 7 days prior to the first dose of medication

Sponsors & Collaborators

• Ixchelsis Limited: lead

Study Sites (1)

Worldwide Clinical Trials Early Phase Services, LLC

San Antonio, Texas, 78217, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2016
• First Posted: November 11, 2016
• Study Start: November 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 13, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)