A Study of the Safety, Tolerability and Pharmacokinetics of Orally-administered GC4702 in Healthy Volunteers

NCT03096756 | Completed Phase 1

• 1 other identifier: GTO-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1 study will test the safety, tolerability and pharmacokinetics of a single dose of GC4702 when given as an oral tablet. This study will compare capsules containing a dry powder or gel suspension of GC4702 when given orally to a similar drug called GC4419 which will be given as an intravenous infusion. This study will also assess the effect of food on the GC4702 effects.

Conditions

Healthy Volunteer

Keywords

Oral Formulation; Food Effect; Superoxide Dismutase; Single Ascending Dose; GC4702; Bioavailability; Pharmacokinetics; Active Comparator

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events and Laboratory Abnormalities

  Number of Participants With Treatment-Emergent Adverse Events and/or Laboratory Abnormalities.

  From randomization through 4 days post last dosing in Active Phase of each cohort.

Study Arms (2)

Part 1: Single Ascending Dose Escalation GC4702

OTHER

Serially increase dose escalation of orally formulated GC4702 or placebo (6:2 ratio), preceded by single dose of active comparator, GC4419 IV.

Drug: GC4702 dry powder; Drug: GC4702 lipid suspension; Other: GC4419 IV; Other: Placebo Dry Powder; Other: Placebo lipid suspension

Part 2: Food Effect Study

EXPERIMENTAL

Following Part 1 dose find, single dose level of GC4702 administered under fasting for and fed condition.

Other: Fed Condition; Other: Fasting Condition; Drug: GC4702 lipid suspension - Part 2

Interventions

GC4702 dry powder DRUG

5 mg GC4702 mixed with approximately 270 mg of Prosolv 90 LM - SMCC (siliconized microcrystalline cellulose). Planned dose levels of GC4702 encapsulated dry powder formulation are 50, 100, and 150 mg

Part 1: Single Ascending Dose Escalation GC4702

GC4702 lipid suspension DRUG

112 mg GC4702 mixed with Miglyol 812 plus 0.5% by weight BHA plus 1% by weight of Aerosil 200. Planned dose levels of GC4702 encapsulated lipid suspension formulation are 112, 224, and 336, 448, and 560 mg

Part 1: Single Ascending Dose Escalation GC4702

GC4419 IV OTHER

infused IV as a single dose of 27 mg (3 mL GC4419 at 9 mg/mL) in 247 mL normal (0.9%) saline, totaling 250 mL, over a 60minute period using a programmable pump.

Part 1: Single Ascending Dose Escalation GC4702

Placebo Dry Powder OTHER

Product matches appearance of the GC4702 dry powder formulation. The Placebo will be 500 mg Miglyol 812 oil containing up to 1% of colloidal silicon dioxide in size 1 capsule.

Part 1: Single Ascending Dose Escalation GC4702

Placebo lipid suspension OTHER

Product matches appearance of the GC4702 lipid suspension formulation. The Placebo will be 500 mg Miglyol 812 oil containing up to 1% of colloidal silicon dioxide in size 1 capsule.

Part 1: Single Ascending Dose Escalation GC4702

Fed Condition OTHER

with 240 mL (8 fluid ounces) of tap water following a high calorie/high fat meal. Subjects assigned to the fed condition will receive a standard meal per U.S. FDA guidelines7 consisting of high calorie/high fat meal prior to dosing consisting of total calories of 800-1000 of which 150, 250 and 500-600 calories are from protein, carbohydrate and fat, respectively.

Part 2: Food Effect Study

Fasting Condition OTHER

For the fasting condition, GC4702 will be administered following an overnight fast of at least 10 hours, with 240 mL (8 fluid ounces) of water. No food will be allowed for at least 4 hours post-dose. Water will be allowed as desired except for one hour before and after drug administration.

Part 2: Food Effect Study

GC4702 lipid suspension - Part 2 DRUG

Two single doses of GC4702 (dose level to be selected based on Part 1 results), separated by a 7-day washout period

Part 2: Food Effect Study

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy men and women, age 18 and 50 years
• Body Mass Index (BMI) 18 to 32 kg/m2, and weighing at least 50 kg at screening.
• Blood pressure and heart rate within normal limits
• Non-lactating, non-pregnant female, confirmed by urine pregnancy screening and willing to use acceptable methods of birth control, per medical and institutional practice.

You may not qualify if:

• History of any chronic disease; or significant medical condition within three months, including but not limited to human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C
• Use of any prescription or over-the-counter medication within one week prior to baseline
• Anticipated need for any medication during the course of the study, with the exception of contraceptive and hormone replacement therapy
• Use of any medications that at risk for causing a precipitous decrease in blood pressure, (e.g., nitrates or erectile dysfunction drugs, from 24 hours prior to screening and throughout participation in the study)
• Use of any vitamin or mineral supplement 24 hours prior to dosing, or anticipated use of any vitamin or mineral supplement throughout the duration of the study;
• History of substance abuse, drug addiction, or alcoholism within 3 years prior to Baseline and/or the inability to abstain from alcohol, or drug use from 48 hours prior to the administration of study drug and throughout the duration of the study as confirmed by toxicology screens during Screening and at Baseline
• History of smoking or any use of a tobacco product within six months prior to Baseline and/or the inability to abstain from tobacco or caffeine use from 48 hours prior to the administration of study drug and throughout the duration of the study.
• Donation of blood or blood products within 30 days prior to the Baseline
• Subject has previously participated in this study.

Sponsors & Collaborators

• Galera Therapeutics, Inc.: lead
• INC Research Australia Pty Ltd: collaborator
• Nucleous Network: collaborator

Study Sites (1)

Nucleus Network Limited

Melbourne, Victoria, 3004, Australia

Location

Related Publications (1)

• Squillace S, Salvemini D. Nitroxidative stress in pain and opioid-induced adverse effects: therapeutic opportunities. Pain. 2022 Feb 1;163(2):205-213. doi: 10.1097/j.pain.0000000000002347. No abstract available.

  PMID: 34145168 DERIVED

Study Officials

• Jon T Holmlund, MD

  Galera Therapeutics, Inc.

  STUDY CHAIR

• Jason Lickliter, MBBS, PhD, FRACP

  Nucleus Network

  PRINCIPAL INVESTIGATOR

• David Fuller, MD

  Syneos Health

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2017
• First Posted: March 30, 2017
• Study Start: July 26, 2016
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 4, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)