A Two Part Study to Assess Safety, PK, PD, and Food Effect of Oral HTL0016878

NCT03244228 | Completed Phase 1

• 3 other identifiers: HTL0016878-1012017-001385-2616-028
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1, first in human, two-part, single centre, placebo-controlled, single and multiple ascending dose trial in healthy younger and elderly adult subjects, with an open-label, randomised, crossover arms to assess the effect of food on bioavailability.

Conditions

Healthy

Keywords

First in human; Multiple ascending dose; Single ascending dose

Outcome Measures

Primary Outcomes (6)

• Treatment emergent adverse events (TEAEs)

  Safety and Tolerability

  Baseline up to 14 days post dose

• Physical examinations

  Safety and Tolerability

  Baseline up to 14 days post dose

• vital signs (Heart Rate and Blood pressure)

  Safety and Tolerability

  Baseline up to 14 days post dose

• Laboratory safety assessment

  Safety and Tolerability

  Baseline up to 14 days post dose

• ECG

  Safety and Tolerability

  Baseline up to 14 days post dose

• Columbia- suicide severity rating scale (C-SSRS)

  Safety and Tolerability

  Baseline up to 14 days post dose

Secondary Outcomes (6)

• Maximum plasma concentration (Cmax) of HTL0016878

  Baseline up to 14 days post dose

• Time to Maximum plasma concentration (Tmax) of HTL0016878

  Baseline up to 14 days post dose

• Area under the curve of HTL0016878

  Baseline up to 14 days post dose

• Half-life (t1/2) of HTL0016878

  Baseline up to 14 days post dose

• Amount excreted in urine (Ae) of HTL0016878

  Baseline up to 14 days post dose

Study Arms (5)

Part 1a SAD HTL0016878/Placebo

EXPERIMENTAL

In Part 1a, single ascending doses of HLT0016878 or matching placebo will be administered to groups of 12 subject each (9 active, 3 placebo). Each subject will have up to four treatment sessions separated by an appropriate wash-out. Healthy, young, male subjects.

Drug: HTL0016878; Drug: Placebo - Concentrate

Part 1b single dose HTL0016878

EXPERIMENTAL

In Part 1b, a single dose of HTL0016878 will be administered to 6 subjects on two occasions: once in the fasted and once the fed state. This will be open-label. Healthy, young, male or female subjects.

Drug: HTL0016878

Part 1c single dose HTL0016878

EXPERIMENTAL

In Part 1c, a single dose of HTL0016878 will be administered to up to 6 (optional up to 12) healthy elderly subjects This will be open-label. Healthy, elderly, male subjects.

Drug: HTL0016878

Part 2a MAD HTL0016878/Placebo

EXPERIMENTAL

In Part 2a, multiple doses of HTL0016878 will be administered to up to 5 cohorts (N=8, 6 active, 2 placebo) during one study session of 7 days. Healthy, young, male or female subjects.

Drug: HTL0016878; Drug: Placebo - Concentrate

Part 2b MAD HTL0016878/Placebo

EXPERIMENTAL

In Part 2b, multiple doses of HTL0016878 will be administered to up to 3 cohorts of healthy, elderly subjects (N=8, 6 active, 2 placebo) during one study session of 7 days. Healthy, young, male or female subjects.

Drug: HTL0016878; Drug: Placebo - Concentrate

Interventions

HTL0016878 DRUG

Oral solution

Part 1a SAD HTL0016878/Placebo; Part 1b single dose HTL0016878; Part 1c single dose HTL0016878; Part 2a MAD HTL0016878/Placebo; Part 2b MAD HTL0016878/Placebo

Placebo - Concentrate DRUG

Matching placebo

Part 1a SAD HTL0016878/Placebo; Part 2a MAD HTL0016878/Placebo; Part 2b MAD HTL0016878/Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Normotensive 18-55 year old (Parts 1a, 1b and 2a only) or 65+ year old (Parts 1c and 2b) male (all parts) or female (parts 1b, 2a and 2b only) volunteers with a body mass index 18-32kg/m².
• Healthy on the basis of a clinical history, physical examination, electrocardiogram (ECG), vital signs, heart rate (part 1a only), exercise history (part 1a only), and laboratory tests of blood and urine.
• Willingness to comply with requirements or the trial, including contraception requirements.
• Able to give fully informed consent.

You may not qualify if:

• Positive tests for hepatitis B \& C, HIV
• severe adverse reaction to any drug
• sensitivity to trial medication
• drug or alcohol abuse
• smoking
• use of medication that inhibits CYP2D6 within previous 21 days or other prescribed and over-the-counter medication and herbal remedies within previous 21 days before dosing (with the exception of acetaminophen, contraceptive medications and hormone replacement therapy), unless the principal investigator (PI) considers that it would not interfere with trial
• participation in other clinical trials of unlicensed medicines in the previous 3 months, or regularly take part in more than 4 studies a year
• loss of more than 500 mL blood in the previous 3 months
• vital signs, QTcF interval or laboratory values outside the acceptable range
• poor metabolizers of CYP2D6 (apart from one optional cohort in Part 1a, which may enrol poor metabolizers only)
• clinically relevant abnormal findings at the screening assessment
• acute or chronic illness
• history of epilepsy or seizures
• clinically relevant abnormal medical history or concurrent medical condition
• disease associated with cognitive impairment and/or psychosis

Sponsors & Collaborators

• Nxera Pharma UK Limited: lead
• Allergan: collaborator

Study Sites (1)

Hammersmith Medicines Research

London, Hammersmith, NW10 7EW, United Kingdom

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: August 9, 2017
• Study Start: August 25, 2017
• Primary Completion: September 23, 2019
• Study Completion: September 23, 2019
• Last Updated: November 29, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)