Clinical trial NCT03244228: A Two Part Study to Assess Safety, PK, PD, and Food Effect of Oral HTL0016878
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: First in human
Multiple ascending dose
Single ascending dose
Lead sponsor: Nxera Pharma UK Limited
Sponsor class: INDUSTRY
Collaborators: name: Allergan
First posted: 2017-08-09
Enrollment: 120
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Treatment emergent adverse events (TEAEs)
timeFrame: Baseline up to 14 days post dose
measure: Physical examinations
timeFrame: Baseline up to 14 days post dose
measure: vital signs (Heart Rate and Blood pressure)
timeFrame: Baseline up to 14 days post dose
measure: Laboratory safety assessment
timeFrame: Baseline up to 14 days post dose
measure: ECG
timeFrame: Baseline up to 14 days post dose
measure: Columbia- suicide severity rating scale (C-SSRS)
timeFrame: Baseline up to 14 days post dose
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of HTL0016878
timeFrame: Baseline up to 14 days post dose
measure: Time to Maximum plasma concentration (Tmax) of HTL0016878
timeFrame: Baseline up to 14 days post dose
measure: Area under the curve of HTL0016878
timeFrame: Baseline up to 14 days post dose
measure: Half-life (t1/2) of HTL0016878
timeFrame: Baseline up to 14 days post dose
measure: Amount excreted in urine (Ae) of HTL0016878
timeFrame: Baseline up to 14 days post dose
measure: Fraction of dose eliminated unchanged on urine (fe/F) of HTL0016878
timeFrame: Baseline up to 14 days post dose
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Hammersmith Medicines Research
state: Hammersmith
Study officials:
References: