NCT03785054

Brief Summary

This is the first time HTL0014242 will be administered to humans. The principal aim of this study is to obtain safety and tolerability data when HTL0014242 is administered orally as single doses to healthy subjects. This information, together with the pharmacokinetics data, will help establish the doses and dosing regimen suitable for future studies in patients

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
71

participants targeted

Target at P75+ for phase_1 healthy

Timeline
Completed

Started Nov 2018

Longer than P75 for phase_1 healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 14, 2018

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

December 13, 2018

Completed
11 days until next milestone

First Posted

Study publicly available on registry

December 24, 2018

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 11, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 11, 2021

Completed
Last Updated

April 29, 2021

Status Verified

April 1, 2021

Enrollment Period

2.3 years

First QC Date

December 13, 2018

Last Update Submit

April 27, 2021

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

  • Number of treatment related adverse event, including abnormal laboratory events

    All AEs, including clinical laboratory, vitals signs, body temperature, respiratory rate, physical examinations and ECGs will be analyzed in all subjects receiving HTL0014242

    Day -1 to follow up (7-14 days after discharge)

Secondary Outcomes (6)

  • Maximum observed plasma concentration (Cmax)

    predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours postdose

  • Area under the curve (AUC) from time 0 to 24 hours postdose (AUC0-24h)

    predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours postdose

  • time to reach the maximum observed plasma concentration (tmax)

    predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours postdose

  • Area under the curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC0-tlast)

    predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours postdose

  • Area under the curve (AUC) from time 0 extrapolated to infinity (AUC0-∞)

    predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours postdose

  • +1 more secondary outcomes

Study Arms (9)

Cohort 1

EXPERIMENTAL

6 subjects receiving a single dose of 1 mg capsule HTL0014242 and 2 subjects receiving matching placebo oral capsule

Drug: HTL0014242Drug: Placebo oral capsule

Cohort 2

EXPERIMENTAL

6 subjects receiving single dose of HTL0014242 and 2 subjects receiving matching placebo oral capsule. The dose of HTL0014242 selected in an escalating manner following review of safety and tolerability data from the previous lower dose level.

Drug: HTL0014242Drug: Placebo oral capsule

Cohort 3

EXPERIMENTAL

6 subjects receiving single dose of HTL0014242 and 2 subjects receiving matching placebo oral capsule. The dose of HTL0014242 selected in an escalating manner following review of safety and tolerability data from the previous lower dose level.

Drug: HTL0014242Drug: Placebo oral capsule

Cohort 4

EXPERIMENTAL

6 subjects receiving single dose of HTL0014242 and 2 subjects receiving matching placebo oral capsule. The dose of HTL0014242 selected in an escalating manner following review of safety and tolerability data from the previous lower dose level.

Drug: HTL0014242Drug: Placebo oral capsule

Cohort 5

EXPERIMENTAL

6 subjects receiving single dose of HTL0014242 and 2 subjects receiving matching placebo oral capsule. The dose of HTL0014242 selected in an escalating manner following review of safety and tolerability data from the previous lower dose level.

Drug: HTL0014242Drug: Placebo oral capsule

Cohort 6

EXPERIMENTAL

6 subjects receiving single dose of HTL0014242 and 2 subjects receiving matching placebo oral capsule. The dose of HTL0014242 selected in an escalating manner following review of safety and tolerability data from the previous lower dose level.

Drug: HTL0014242Drug: Placebo oral capsule

Cohort 7

EXPERIMENTAL

6 subjects receiving single dose of HTL0014242 and 2 subjects receiving matching placebo oral capsule. The dose of HTL0014242 selected in an escalating manner following review of safety and tolerability data from the previous lower dose level.

Drug: HTL0014242Drug: Placebo oral capsule

Cohort 8

EXPERIMENTAL

6 subjects receiving single dose of HTL0014242 and 2 subjects receiving matching placebo oral capsule. The dose of HTL0014242 selected in an escalating manner following review of safety and tolerability data from the previous lower dose level.

Drug: HTL0014242Drug: Placebo oral capsule

Cohort 9

EXPERIMENTAL

6 subjects receiving single dose of HTL0014242 and 2 subjects receiving matching placebo oral capsule. The dose of HTL0014242 selected in an escalating manner following review of safety and tolerability data from the previous lower dose level.

Drug: HTL0014242Drug: Placebo oral capsule

Interventions

HTL0014242DRUG

HTL0014242 is a selective negative allosteric modulator (NAM) for the metabotropic glutamate (mGlu) receptor 5 subtype (mGlu5)

Cohort 1Cohort 2Cohort 3Cohort 4Cohort 5Cohort 6Cohort 7Cohort 8Cohort 9
Placebo oral capsuleDRUG

Placebo treatment

Cohort 1Cohort 2Cohort 3Cohort 4Cohort 5Cohort 6Cohort 7Cohort 8Cohort 9

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy males or females of any race, between 18 and 55 years of age, inclusive.
  • Body mass index between 18.0 and 30.0 kg/m2, inclusive, with a body weight of at least 50.0 kg.
  • In good physical and mental health, including no clinically significant findings from medical history, physical examination, psychiatric examination, 12 lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[eg, suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at screening or check in as assessed by the investigator (or designee).
  • Females who are not pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
  • Has clinical laboratory test results within the reference ranges of the testing laboratory, with the exception of results outside the reference ranges that are deemed not clinically significant by the Investigator (or designee) at screening and check-in.
  • Has supine blood pressure and pulse rate within the following ranges after 5 minutes rest: systolic blood pressure 90 to 140 mmHg, diastolic blood pressure 40 to 90 mmHg, and pulse rate 45 to 90 bpm.
  • Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

You may not qualify if:

  • Past or current history of any mental, behavioural, or neurodevelopmental disorder as defined by the tenth revision of the International Classification of Diseases (ICD-10)16 including, but not limited to, diagnoses of: organic, including symptomatic, mental disorders (F00-F09); mental and behavioural disorders due to psychoactive substance use (F10-F19); schizophrenia, schizotypal, and delusional disorders (F20-F29); mood \[affective\] disorders (F30-F39); neurotic, stress-related, and somatoform disorders (F40-F48); disorders of adult personality and behaviour (F60-F69).
  • Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, gastrointestinal, neurological, respiratory, or endocrine disorder, as determined by the Investigator (or designee).
  • Active or history of cardiovascular or cerebrovascular disease, including hypertension, angina, ischaemic heart disease, transient ischaemic attacks, bundle branch block, evidence of myocardial ischaemia, stroke, and peripheral arterial disease sufficient to cause symptoms and/or require therapy to maintain stable status.
  • History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
  • Active neoplastic disease or history of any neoplastic disease within 5 years of screening (except for basal or squamous cell carcinoma of the skin or carcinoma in situ that has been definitely treated with standard of care).
  • Active infection (eg, sepsis, pneumonia, abscess) or a serious infection (eg, resulting in hospitalisation or requiring parenteral antibiotic treatment) within 6 weeks prior to dosing.
  • History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
  • Any of the following at screening and/or predose:
  • QT interval corrected for heart rate using Fridericia's method (QTcF) \>450 ms confirmed by repeat measurement
  • QRS duration \>110 ms confirmed by repeat measurement
  • PR interval \>220 ms confirmed by repeat measurement
  • findings which would make QTc measurements difficult or QTc data uninterpretable
  • history of additional risk factors for torsades de pointe (eg, heart failure, hypokalemia, family history of long QT syndrome).
  • History of alcoholism or drug/chemical abuse.
  • Alcohol consumption of \>14 units (females) and \>21 units (males) per week. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
  • +24 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Covance

Leeds, West Yorkshire, LS2 9LH, United Kingdom

Location

Study Officials

  • Jim Bush, MBChB, PhD

    Covance

    PRINCIPAL INVESTIGATOR

  • Hamzah Malik

    Covance

    STUDY DIRECTOR

  • Robert Holland, BMBCh, DPhil

    Heptares Therapeutics Ltd

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
• Placebo capsules will be identical in appearance to the HTL0014242 capsules
Purpose
BASIC SCIENCE
Intervention Model
SEQUENTIAL
Model Details: Single ascending dose
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 13, 2018

First Posted

December 24, 2018

Study Start

November 14, 2018

Primary Completion

March 11, 2021

Study Completion

March 11, 2021

Last Updated

April 29, 2021

Record last verified: 2021-04

Data Sharing

IPD Sharing
Will not share

Locations

GB(1)