Genetic Variability in CYP2D6 in U.S Active Duty Population

• Status: Completed
• Trial end date: 2017-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The investigator proposes to 2D6 (Cytochrome P-450 Isoenzyme 2D6) genotype and phenotype a group of active duty service members and assess the effects on primaquine metabolism.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Walter Reed Army Institute of Research (WRAIR)
• Treatments: Primaquine

Criteria

Inclusion criteria:

• Active duty Service member, (male or female) 18 to 60 years of age (inclusive) at the time of enrollment

• Written informed consent for phase 1 must be obtained

• Written informed consent for phase 2 must be obtained from the subject before the screening procedures

• Free of significant health problems as established by medical history, laboratory and clinical examination before entering the study

• If the subject is female, she must be of non-childbearing potential (either surgically sterilized or one year post-menopausal) or, if of childbearing potential, she must be capable of preventing pregnancy, have a negative pregnancy test at the time of the administration of primaquine , and must agree to continue such precautions until 48 hours after primaquine administration.

• Normal (non-deficient) G6PD (glucose-6-phosphate dehydrogenase) phenotype (range: 4.6 to 13.5 units/gm hemoglobin)

• Subjects must obtain approval from his or her supervisor per Walter Reed Army Institute of Research (WRAIR) Policy 06-15 in order to be participate in the PQ PK portion of phase 2

Exclusion criteria:

• Use of any investigational or non-registered drug within 30 days preceding the primaquine dosing.

• Pregnant (positive urine β-HCG) or nursing at screening or plans to become pregnant or nurse from the time of enrollment until 48 hours after primaquine dosing.

• Allergy to primaquine

• Use of medications known to cause drug interactions with primaquine or CYP2D6

• Acute or chronic, clinically significant, pulmonary, cardiovascular, hepatic, neurologic, or renal functional abnormality, as determined by history, physical examination, and laboratory evaluation

• History of hemolytic anemia

• Any abnormal baseline laboratory screening tests listed below (normal values are defined by the current Quest Diagnostics reference guide on file in the CTC):

• ALT (alanine aminotransferase)above normal range

• Glomerular filtration rate (GFR) below normal range for the subject's ethnicity

• Hemoglobin below normal range

• Hepatomegaly, right upper quadrant abdominal pain or tenderness

• Suspected or known current alcohol abuse as determined from the medical history or by physical examination

• Use of any drugs that may cause hemolytic anemia and/or bone marrow suppression such as quinacrine, dapsone, rifampin, colchicine, ribavirin, penicillamine and sulfonamides.

• Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study