Overview of phase I trials of 2',3'-dideoxyinosine (ddI) conducted on adult patients. 1990

M Rozencweig, and C McLaren, and M Beltangady, and J Ritter, and R Canetta, and L Schacter, and S Kelley, and C Nicaise, and L Smaldone, and L Dunkle
Bristol-Myers Squibb Company, Pharmaceutical Research and Development Division, Wallingford, Connecticut 06492-7660.

Ninety-two adult patients with AIDS or severe AIDS-related complex were treated with 2',3'-dideoxyinosine (didanosine; ddI) at dosages ranging from 0.8 to 66.0 mg/(kg.d) for at least 6 weeks in phase I trials. Potentially beneficial changes in weight (40% of patients), clinical signs or symptoms (40% of patients), CD4+ cell counts (25% of patients), and serum levels of HIV p24 antigen (50% of antigen-positive patients) were reported. Response rates tended to be higher among patients with AIDS-related complex and among those who had not received prior zidovudine therapy. A major response (improvement in at least one clinical parameter and in at least one laboratory marker) occurred in 29% of patients, and rates of major response tended to be higher in patients receiving higher dosages. The primary dose-limiting toxicity observed was peripheral neuropathy, which was observed with increasing frequency in patients receiving greater than 20 mg/(kg.d). Of the other adverse effects, pancreatitis was possibly dose-dependent and hyperuricemia (without clinical gout) occurred only at high doses. Dosages of 250 mg and 375 mg of ddI twice daily will be used in extended phase II/III studies.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009894 Opportunistic Infections An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. Infection, Opportunistic,Infections, Opportunistic,Opportunistic Infection
D010195 Pancreatitis INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis. Acute Edematous Pancreatitis,Acute Pancreatitis,Pancreatic Parenchyma with Edema,Pancreatic Parenchymal Edema,Pancreatitis, Acute,Pancreatitis, Acute Edematous,Peripancreatic Fat Necrosis,Acute Edematous Pancreatitides,Acute Pancreatitides,Edema, Pancreatic Parenchymal,Edematous Pancreatitides, Acute,Edematous Pancreatitis, Acute,Fat Necrosis, Peripancreatic,Necrosis, Peripancreatic Fat,Pancreatic Parenchymal Edemas,Pancreatitides, Acute,Pancreatitides, Acute Edematous,Parenchymal Edema, Pancreatic,Peripancreatic Fat Necroses
D010523 Peripheral Nervous System Diseases Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. Peripheral Nerve Diseases,Peripheral Neuropathies,PNS (Peripheral Nervous System) Diseases,PNS Diseases,Peripheral Nervous System Disease,Peripheral Nervous System Disorders,Nerve Disease, Peripheral,Nerve Diseases, Peripheral,Neuropathy, Peripheral,PNS Disease,Peripheral Nerve Disease,Peripheral Neuropathy
D004341 Drug Evaluation Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. Evaluation Studies, Drug,Drug Evaluation Studies,Drug Evaluation Study,Drug Evaluations,Evaluation Study, Drug,Evaluation, Drug,Evaluations, Drug,Studies, Drug Evaluation,Study, Drug Evaluation
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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