Clinical Trials Roundup—Week of 11/09

Gliatech Initiates Human Trials For Histamine Antagonist

Gliatech Inc. has initiated Phase I human clinical trials for GT 2331, its selective histamine H3 receptor antagonist. Gliatech has targeted the development of GT 2331 for central nervous systems diseases such as attention deficit hyperactive disorder (ADHD), Alzheimer's disease and/or various sleep disorders.

Histamine is a chemical messenger released from certain neurons in the brain which regulates sleep/wake states and modulates levels of arousal and alertness in the conscious state. The histamine H3 receptor is predominantly found in the brain and regulates the synthesis and release of histamine in the brain. An antagonist to this receptor would lead to enhanced states of arousal and alertness.

For more information: Gliatech, Inc., telephone: 1-888-GLIATECH (888-454-2832).

Viropharma Reports Pleconaril Results In Viral Meningitis Trial

Viropharma, Inc. has announced the results of its preliminary evaluation of the first of four pivotal studies of pleconaril (two in children and two in adults) for the treatment of viral meningitis. The trial was a double-blind, placebo-controlled study of 221 patients, ages 4 to 14 years.

Patients with confirmed enterovirus infection did not achieve a statistically significant reduction in the time to absence of headache. However, statistical significance was achieved in the total morbidity score, a composite measurement of all disease symptoms and the global assessment score, which measures a caregiver's assessment of a patient's illness at a low dose of placebo (2.5 mg/kg).

Endothelin A Receptor Antagonist Reduces PVR And PAP

A Phase IIA clinical trial of Texas Biotechnology Corp.'s TBC11251, an endothelin A receptor antagonist, has identified its ability to reduce pulmonary vascular resistance and pulmonary artery pressure. Positive trends were also seen in other measures of hemodynamics, including cardiac output and no compensatory increase in heart rate was observed.

Endothelin exerts its effects through the activation of endothelin A and endothelin B receptors. Endothelin A receptors are primarily involved in vasoconstriction while endothelin B receptors are vasodilatory via release of nitric oxide (NO).

Diovan Reduces Left Ventricular Hypertrophy In Hypertensive Patients

A new study shows that Novartis' angiotensin II receptor blocker, Diovan (valsartan), reduces left ventricular hypertrophy (LVH), a powerful independent risk factor for cardiovascular disease, in hypertensive patients.

Diovan provides a highly specific blockade of angiotensin II at the AT(1) receptor. When the hormone angiotensin II binds to the AT(1) receptor, it causes negative cardiovascular effects, such as stimulation of myocardial cell proliferation and growth, which can contribute to LVH.

For more information: Anna Frable, Novartis Pharmaceuticals Corporation, 59 Route 10, East Hanover, NJ 07936, telephone: 973-781-5388.

OP-1 Enhances Motor Skills Recovery Up To 3 Days Following Stroke

Creative BioMolecules, Inc. has announced that OP-1, its unique approach to stroke, can enhance motor skills recovery in preclinical studies when administered up to 3 days following stroke. OP-1, a morphogenic protein-based stroke therapy, appears to enhance the body's natural regenerative processes by promoting the formation of new connections between nerve cells.

For more information: Creative BioMolecules, Inc., 101 Huntington Avenue, Suite 2400, Boston, MA 02199, USA. Telephone: 617-912-2955.

GenVec Completes Patient Enrollment In Angiogenesis Trial

GenVec, Inc. has completed patient enrollment in its Phase I clinical study at the New York Hospital-Cornell Medical Center to evaluate the safety of its lead investigational compound, AdGVVEGF121.10.

AdGVVEGF121.10 is being investigated for its potential to induce angiogenesis, or new blood vessel formation, in tissues with inadequate blood flow. The Phase I study will investigate the compound's potential use in patients with coronary artery disease and patients with peripheral vascular disease under the terms of a collaboration with the Parke-Davis pharmaceutical division of Warner-Lambert Company.

For more information: GenVec, Inc., telephone: 301-816-0442.

EECP Patients Showing Continued Improvement 12 Months After Treatment

Vasomedical, Inc. has reported that patients with angina who received Enhanced External Counterpulsation (EECP) treatment during a multicenter clinical trial showed continued functional improvement 12 months later, whereas a similar group of patients given a sham treatment reported no significant change in the same period.

For more information: Anthony E. Peacock, Vasomedical, Inc., telephone: 516-997-4600, ext. 120.

Further Testing Required To Determine Full Effects Of AIT-082

NeoTherapeutics, Inc. and the Alzheimer's Disease Cooperative Study (ADCS) have reported the results of a Phase 1 clinical trial on NeoTherapeutics' drug compound AIT-082 (Neotrofin, leteprinim potassium). Subjects tended to perform better on tests of memory and concentration when they received AIT-082 than when they received placebo, the study concludes. Due to the small number of people in this study (8 healthy elderly volunteers), further testing will be required before the effects of AIT-082 on the human memory can be established.

AIT-082 is a novel small molecule that, in animals, crosses the blood-brain barrier to regenerate nerve function by increasing levels of neurotrophic growth factors and causing nerve sprouting in the brain. Pre-clinical studies in animals have demonstrated that AIT-082 improves memory in aged animals and in animals with neurological deficits.

For more information: NeoTherapeutics, Inc., 157 Technology Drive, Irvine, CA 92618, USA. Tel: 949-788-6700. Fax: 949-788-6706

Fosamax Found To Increase Bone Mineral Density In Men

New data presented at the annual meeting of the American College of Rheumatology showed the investigational use of Fosamax (alendronate sodium) in men stopped bone loss and increased bone mineral density (BMD) at the spine and hip, two common sites of osteoporotic fracture. The men in the study all were at risk of osteoporosis and future fracture due to chronic use of glucocorticoids (commonly referred to as corticosteroids, or steroids).

Fosamax is a nonhormonal, bone-specific aminobisphosphonate that is currently indicated for the treatment of osteoporosis in postmenopausal women. It acts as a specific inhibitor of osteoclast-mediated bone resorption by binding to the hydroxyapatite found in bone.

For more information: Donna Cary, Merck, telephone: 215-652-5628.

BMS Launches Phase III Trials Of Lobucavir

Bristol-Myers Squibb Co. has launched large-scale, phase III clinical trials of Lobucavir that will enroll 1,000 chronically-infected hepatitis B (HBV) patients in 255 sites across the United States, Europe, Canada, Latin America and Asia. Lobucavir is a broad-spectrum nucleoside analogue antiviral with activity against HBV and herpes viruses.

For more information: Bristol-Myers Squibb Co., 311 Pennington & Rocky Hill Road, Pennington, NJ 08534-2130.

Adenosine May Reduce Infarct In Heart Attacks By Up To 67%

Medco Research's Phase II study has shown that when adenosine is combined with clot busters, such as tissue plasminogen activator and streptokinase to treat a heart attack, the area of damage (or infarct) may be reduced by as much as an additional 67 percent over clot busters alone.

Adenosine is a naturally occurring hormone-like substance found in virtually every cell in the body that protects the body against the effects of oxygen deprivation. It protects the heart by triggering a number of actions such as increasing blood supply and/or decreasing oxygen demand during episodes of cardiac ischemia.

For more information: Mike Freeman, Medco Research, telephone: 919-549-8114.

Can Heart Function Be Altered By Gene Transfer?

An in vivo animal study has found that inserting a certain gene into the heart triggers a robust increase in the production of the enzyme that drives the heart to beat more strongly, implying that heart function can be altered by gene transfer.

Collateral Therapeutics researchers found that increasing the production of AC (adenylate cyclase) using transgenic techniques, safely and effectively boosts cAMP, which is ultimately responsible for commanding the heart to pump, resulting in improved cardiac function and increased ability of the heart to contract.

For more information: Collateral Therapeutics, telephone: 1-800-758-5804, ext. 128401.

Arava Slows Rheumatoid Arthritis In Phase III Trial

Hoechst Marion Roussel's oral rheumatoid arthritis medication, Arava (leflunomide), significantly slowed disease progression and improved physical function in a Phase III, placebo-controlled clinical trial involving 482 rheumatoid arthritis patients, the company reports.

Arava is a disease-modifying antirheumatic drug (DMARD) that was approved for marketing by the U.S. Food and Drug Administration in September for the treatment of adults with active rheumatoid arthritis.

For more information: Julie L. Gladman, 816-966-4274, or Charles F. Rouse III, 1-800-778-5138, both of Hoechst Marion Roussel.

Nastech Completes Study Program Of Motion Sickness Treatment

Nastech Pharmaceutical Co. has completed its clinical study program for use of intranasal scopolamine for prevention and treatment of motion sickness. Prior to filing a New Drug Application for intranasal scopolamine during the first quarter of 1999, the company plans to have a pre-NDA meeting with the FDA that may potentially result in a much smoother and more efficient review process.

For more information: Andrew Zinzi, Nastech Pharmaceutical Company, Inc., telephone: 516-273-0101.

IntraBiotics Begins Trial Of Potential Treatment For Oral Mucositis

IntraBiotics Pharmaceuticals, Inc. has begun a Phase II clinical trial of Protegrin IB-367, a potential new treatment for oral mucositis, a severely debilitating ulcerative condition resulting from tissue damage caused by cancer therapies and invasion of that tissue by microorganisms.

The goal of the study is to determine whether Protegrin IB-367 can reduce the incidence, severity, and duration of oral mucositis in patients treated with ablative doses of chemotherapy. IB-367 is a synthetic analog of the protegrin family of mammalian antimicrobial peptides.

For more information: Kenneth J. Kelley, IntraBiotics Pharmaceuticals, Inc., telephone: 650-526-6800.