Relative Bioavailability of HTL0018318 Oral Aqueous Solution Versus Capsules

NCT02958696 | Completed Phase 1

• 3 other identifiers: HTL0018318-1042016-003313-9916-024
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

HTL0018318 is a selective muscarinc M1 agonist. This study is a phase I, open label, randomised, crossover, single dose, trial in healthy volunteers to compare the relative bioavailability of HTL0018318 when given by oral aqueous solution and in capsule formulation.

Conditions

Bioavailability and Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Maximum plasma concentration (Cmax) of HTL0018318

  Comparison of bioavailability in plasma

  Predose to 168h post dose

• Area under the curve (AUC) of HTL0018318

  Comparison of bioavailability in plasma

  Predose to 168h post dose

Secondary Outcomes (12)

• Time to maximum concentration (tmax)

  Predose to 168h post dose

• Half-life (t1/2)

  Predose to 168h post dose

• Apparent volume of distribution (Vz/F)

  Predose to 168h post dose

• Apparent clearance (CLp/F)

  Predose to 168h post dose

• Amount excreted in urine (Ae)

  Predose to 168h post dose

Study Arms (3)

HTL0018318 low dose

ACTIVE COMPARATOR

low dose aqueous solution and/or equivalent low dose capsule

Drug: HTL0018318

HTL0018318 mid dose

ACTIVE COMPARATOR

mid dose aqueous solution and/or equivalent mid dose capsule

Drug: HTL0018318

HTL0018318 high dose

ACTIVE COMPARATOR

high dose aqueous solution and/or equivalent high dose capsule(s)

Drug: HTL0018318

Interventions

HTL0018318 DRUG

Two single doses of active drug (low, mid or high dose either as aqueous solution or capsule) separated by a washout of at least 12 days.

HTL0018318 high dose; HTL0018318 low dose; HTL0018318 mid dose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female healthy volunteer.
• Aged 18-55 years.
• A body mass index (Quetelet index) in the range 18.0-34.
• Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
• Willingness to comply with the contraception requirements of the trial.
• Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate.
• Willingness to give written consent to have data entered into The Overvolunteering Prevention System.

You may not qualify if:

• Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.
• QTcF outside range 300-450 msec for males, and 300-470 msec for females at resting ECG at screening and baseline.
• Family history of unexplained sudden death, or sudden death due to long QT syndrome.
• Clinically relevant abnormal findings based on 24 h ECG Holter monitoring during screening, including any of the following: \> 200 ventricular ectopic heart beats, ventricular tachycardia, defined as \>= 3 successive ventricular ectopic beats at a rate of \>120 bpm, second degree heart block, sustained cardiac arrhythmias, including atrial fibrillation, complete heart block and supraventricular tachycardia (SVT), any symptomatic arrhythmia except isolated extra systoles.
• Aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT) or total bilirubin \>1.5 x ULN at screening, or other laboratory blood chemistry test results outside the normal reference range unless deemed not clinically significant by the investigator.
• Clinically significant renal insufficiency as indicated by a glomerular filtration rate lower than the age-related L at screening. In the event of a glomerular filtration rate \>80, eligibility may be confirmed by a second measurement.
• Blood pressure and heart rate in supine position at the screening examination outside the ranges 90-140 mm Hg systolic, 50-90 mm Hg diastolic; heart rate 45-100 beats/min. Subject with borderline values can be included if the values are deemed not clinically significant by the investigator.
• Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous.
• Impaired gastrointestinal, endocrine, thyroid, hepatic, cardiovascular, respiratory, haematological, renal or neurological function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness deemed clinically significant by the investigator.
• History of a chronic respiratory condition, such as asthma, recurrent chest infections of chronic obstructive pulmonary disease.
• History of epilepsy or seizures.
• History of a severe allergy. Non-active hayfever is acceptable.
• 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.
• Woman who is pregnant or lactating, or pre-menopausal woman who is sexually active and not using a reliable method of contraception.

Sponsors & Collaborators

• Nxera Pharma UK Limited: lead

Study Sites (1)

Hammersmith Medicines Research

London, NW10 7EW, United Kingdom

Location

Study Officials

• Adeep Puri, MPhil MBBS

  Hammersmith Medicines Research

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 1, 2016
• First Posted: November 8, 2016
• Study Start: October 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: February 3, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)