Effects of Dual Cyclooxygenase-2 and Carbonic Anhydrase Inhibition

Summary

Cyclooxygenase-2 (COX-2) inhibitors have become a common analgesic treatment option for patients with arthritis. However, long-term treatment has been associated with increased cardiovascular risk. With the past withdrawals and rejections of approval for COX-2 inhibitors the treatment options are now very limited.

This translates for example to about 10 million osteoarthritis patients in the US who cannot receive COX-2 inhibitors because of concomitant hypertension. And this exemplifies the unmet medical need to develop and offer safe treatment options for this particular patient population.

This trial investigates pharmacodynamic aspects of CG100649 which is being developed as a novel COX-2 inhibitor. Preclinical data show a dual mechanism of action, which consists of the inhibition of the two enzymes COX-2 and carbonic anhydrase-I/-II (CA-I/II) and through which the cardiovascular risk of COX-2 inhibition might be attenuated.

Conditions

• Healthy Volunteers

Interventions

DRUG

CG100649 (2 mg)

CG100649 capsules: 2 mg, single oral administration (Part 1); CG100649 capsules: dose to be determined, single oral administration (the single CG100649 dose level used in Part 3 will be determined by part 1 and 2).

DRUG

Celecoxib

Celecoxib (Celebrex®) capsules: 200 mg; single oral administration (Part 1 and 3)

DRUG

Placebo capsules

Placebo capsules: 198 mg silicified microcrystalline cellulose + 2 mg talc, multiple oral administrations (Part 1 and 3)

DRUG

Naproxen

Naproxen (Naprosyn®) tablets: 500 mg, single oral administration (Part 3)

DRUG

Acetazolamide

Acetazolamide (generic, immediate release) tablets: 250 mg, single oral administration (Part 3)

DRUG

CG100649 (8 mg)

CG100649 capsules: 8 mg, single oral administration (Part 1); CG100649 capsules: dose to be determined, single oral administration (the single CG100649 dose level used in Part 3 will be determined by part 1 and 2).

Sponsors & Collaborators

• CrystalGenomics, Inc.

  collaborator INDUSTRY

• University of Pennsylvania

  lead OTHER

Principal Investigators

• Garret A FitzGerald, MD · Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine

• Carsten C Skarke, MD · Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine

• William K Schmidt, PhD · CrystalGenomics, Inc.

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2008-10-31

Primary Completion

2013-07-31

Completion

2013-07-31

Countries

• United States

Study Locations