Clinical trial NCT02361034: To Evaluate Safety, Tolerability and Pharmacokinetics of GRC 27864 in Healthy Subjects and Elderly Healthy Subjects
Official title: A Two-Part, Phase I Study of Orally Administered GRC 27864, a Novel, Microsomal Prostaglandin E Synthase-1 Enzyme (mPGES-1) Inhibitor, to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses in Healthy Subjects (Part 1), and of Multiple Doses in Elderly Subjects (Part 2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Safety and pharmacokinetics of drug in healthy volunteers
Lead sponsor: Glenmark Pharmaceuticals S.A.
Sponsor class: INDUSTRY
First posted: 2015-02-11
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is a multiple Ascending dose (MAD) study with GRC 27864 in Healthy and Elderly Subjects.


Eligibility criteria: Inclusion Criteria:

1. Male or female subjects, aged ≥18 to \<55 years (\> 65 years for elderly cohort) at the time of informed consent
2. Body mass index (BMI) within the range 18.5-32 kg/m2 (inclusive); weight must be \>50 kg
3. Subjects who are healthy and free from clinically significant illness or disease
4. Females must be of non-childbearing potential, surgically sterile.
5. Male subjects whose partners are of childbearing potential or have undergone tubal ligation must agree to use 2 highly effective methods of contraception

Exclusion Criteria:

1. Systolic blood pressure (SBP) \<90 mmHg or \>140 mmHg, diastolic blood pressure (DBP) \<45 mmHg or \>90 mmHg, resting pulse rate \<40 beats per minute (bpm) or \>100 bpm
2. Subjects who have the presence of active peptic ulcer disease, gastrointestinal (GI) bleeding, chronic gastritis, inflammatory bowel disease, chronic diarrhoea or positive 13C urea breath/faecal test for Helicobacter pylori at Screening.
3. Subjects with inherited or acquired disorders of platelet function, bleeding or coagulation.
4. Presence of any clinically relevant acute or chronic disease that could interfere with the subject's safety during the clinical study, expose the subject to undue risk.

Primary outcomes:
measure: Number of TEAEs and serious adverse events (SAEs) after multiple oral doses of GRC 27864 in healthy adult and elderly subjects
timeFrame: Baseline upto 42 days after administration of the study drug.
Secondary outcomes:
measure: Maximum Concentration (Cmax) of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.
timeFrame: Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
measure: Time to Maximum Concentration (Tmax) of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.
timeFrame: Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
measure: Area Under Curve [AUC0-t and AUC0-tau] of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.
timeFrame: Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
measure: Half-life (t½) of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.
timeFrame: Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
measure: Volume of distribution (V)/bioavailability (F) of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.
timeFrame: Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
measure: Clearance (CL)/F of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.
timeFrame: Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
measure: Observed accumulation ratio (Rac) of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.
timeFrame: Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
measure: Cerebrospinal fluid (CSF) concentrations of GRC 27864 and its metabolite GRC 27884 (CmaxCSF) following multiple doses to healthy adult subjects
timeFrame: 6 hours, and 24 hours postdose on Day 26
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Covance Clinical Research Unit Ltd
state: Yorkshire
Study officials:
affiliation: Medical Director
name: Jim Bush, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
References: