To Evaluate Safety, Tolerability and Pharmacokinetics of GRC 27864 in Healthy Subjects and Elderly Healthy Subjects

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)

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: GRC 27864

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Yorkshire
    • Leeds, Yorkshire, United Kingdom, LS2 9LH
      • Covance Clinical Research Unit Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo treatment	Drug: Placebo
Active Comparator: GRC 27864; Test treatment GRC 27864	Drug: GRC 27864

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of TEAEs and serious adverse events (SAEs) after multiple oral doses of GRC 27864 in healthy adult and elderly subjects	Baseline upto 42 days after administration of the study drug.

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Concentration (Cmax) of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.	Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
Time to Maximum Concentration (Tmax) of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.	Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
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.	Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
Half-life (t½) of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.	Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
Volume of distribution (V)/bioavailability (F) of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.	Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
Clearance (CL)/F of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.	Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
Observed accumulation ratio (Rac) of GRC 27864 and its metabolite GRC 27884 following multiple doses in healthy adult subjects and elderly subjects.	Predose and postdose from 0.25 to 48 hrs and from Day 1 to day 28
Cerebrospinal fluid (CSF) concentrations of GRC 27864 and its metabolite GRC 27884 (CmaxCSF) following multiple doses to healthy adult subjects	6 hours, and 24 hours postdose on Day 26

Collaborators and Investigators

• Sponsor: Glenmark Pharmaceuticals S.A.
• Investigators: Principal Investigator: Jim Bush, MBChB, PhD, Medical director

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: February 3, 2015
• First Submitted That Met QC Criteria: February 6, 2015
• First Posted (Estimate): February 11, 2015

Study Record Updates

• Last Update Posted (Estimate): December 15, 2015
• Last Update Submitted That Met QC Criteria: December 14, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Safety and pharmacokinetics of drug in healthy volunteers
• Other Study ID Numbers: GRC 27864-102; 2014-001932-13 (EudraCT Number)