We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is currently recruiting participants.
Verified September 2017 by Heptares Therapeutics Limited
Sponsor:
ClinicalTrials.gov Identifier:
NCT03244228
First Posted: August 9, 2017
Last Update Posted: September 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Allergan
Information provided by (Responsible Party):
Heptares Therapeutics Limited
  Purpose
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.

Condition Intervention Phase
Healthy Drug: HTL0016878 Drug: Placebo - Concentrate Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double blind
Primary Purpose: Treatment
Official Title: A Two-part, Randomised, Double-blind, Placebo-controlled Single and Multiple Ascending Dose Study to Assess Safety, Pharmacokinetics and Pharmacodynamics of Oral HTL0016878 in Healthy Younger Adult and Elderly Subjects With a Randomised, Open-label, Crossover Arm to Assess the Effect of Food on Bioavailability of Oral HTL0016878.

Further study details as provided by Heptares Therapeutics Limited:

Primary Outcome Measures:
  • Treatment emergent adverse events (TEAEs) [ Time Frame: Baseline up to 14 days post dose ]
    Safety and Tolerability

  • Physical examinations [ Time Frame: Baseline up to 14 days post dose ]
    Safety and Tolerability

  • vital signs (Heart Rate and Blood pressure) [ Time Frame: Baseline up to 14 days post dose ]
    Safety and Tolerability

  • Laboratory safety assessment [ Time Frame: Baseline up to 14 days post dose ]
    Safety and Tolerability

  • ECG [ Time Frame: Baseline up to 14 days post dose ]
    Safety and Tolerability

  • Columbia- suicide severity rating scale (C-SSRS) [ Time Frame: Baseline up to 14 days post dose ]
    Safety and Tolerability


Secondary Outcome Measures:
  • Maximum plasma concentration (Cmax) of HTL0016878 [ Time Frame: Baseline up to 14 days post dose ]
    Pharmacokinetics

  • Time to Maximum plasma concentration (Tmax) of HTL0016878 [ Time Frame: Baseline up to 14 days post dose ]
    Pharmacokinetics

  • Area under the curve of HTL0016878 [ Time Frame: Baseline up to 14 days post dose ]
    Pharmacokinetics

  • Half-life (t1/2) of HTL0016878 [ Time Frame: Baseline up to 14 days post dose ]
    Pharmacokinetics

  • Amount excreted in urine (Ae) of HTL0016878 [ Time Frame: Baseline up to 14 days post dose ]
    Pharmacokinetics

  • Fraction of dose eliminated unchanged on urine (fe/F) of HTL0016878 [ Time Frame: Baseline up to 14 days post dose ]
    Pharmacokinetics


Estimated Enrollment: 106
Actual Study Start Date: August 25, 2017
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1a SAD HTL0016878/Placebo
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
Oral solution
Drug: Placebo - Concentrate
Matching placebo
Experimental: Part 1b single dose HTL0016878
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
Oral solution
Experimental: Part 1c single dose HTL0016878
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
Oral solution
Experimental: Part 2a MAD HTL0016878/Placebo
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
Oral solution
Drug: Placebo - Concentrate
Matching placebo
Experimental: Part 2b MAD HTL0016878/Placebo
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
Oral solution
Drug: Placebo - Concentrate
Matching placebo

Detailed Description:
This is a first in human single and multiple ascending dose study with the objective to evaluate safety, tolerability, PK, PD, and food effect of HTL0016878 in healthy younger and elderly subjects. Part 1 will assess single doses of HTL0016878 and Part 2 will assess multiple doses of HTL0016878. Part 1 will be divided into 3 sub-parts: Part 1a will assess single ascending doses (SAD) of HTL0016878 in younger adult subjects, Part 1b will evaluate the effect of food on bioavailability of HTL0016878 and part 1c will investigate the effect of age on the PK of HTL0016878. Part 1c will only proceed after review of safety, tolerability and PK data from part 1a. Part 2 will be divided into 2 sub-parts to assess multiple ascending doses (MAD) of HTL0016878 in younger adult (part 2a) and elderly adult (part 2b) subjects. Part 2 will only proceed after review of safety, tolerability and PK data from Parts 1a, b and c.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • recent history of suicidal thoughts or ideation, or insomnia
  • excessive use of caffeine containing beverages, exceeding 8 cups of coffee or equivalent/day and the inability to refrain from the use of caffeine containing beverages whilst on the ward
  • consumption of cranberry, pomegranate, star fruit, grapefruit, pomelos, exotic citrus fruits or Seville oranges (including marmalade and juices made from these fruits) within 3 days before admission; possibility that volunteer will not cooperate
  • pre-menopausal females who are pregnant or lactating, or who are sexually active and not using a reliable method of contraception
  • Objection by the GP.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03244228


Contacts
Contact: Malcolm Boyce, BSc MD FRCP FFPM 020 8961 4130 mboyce@hmrlondon.com

Locations
United Kingdom
Hammersmith Medicines Research Recruiting
London, Hammersmith, United Kingdom, NW10 7EW
Contact: Malcolm Boyce, BSc MD FRCP FFPM    020 8961 4130    mboyce@hmrlondon.com   
Sponsors and Collaborators
Heptares Therapeutics Limited
Allergan
  More Information

Responsible Party: Heptares Therapeutics Limited
ClinicalTrials.gov Identifier: NCT03244228     History of Changes
Other Study ID Numbers: HTL0016878-101
2017-001385-26 ( EudraCT Number )
16-028 ( Other Identifier: HMR )
First Submitted: August 3, 2017
First Posted: August 9, 2017
Last Update Posted: September 7, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Heptares Therapeutics Limited:
First in human
Multiple ascending dose
Single ascending dose