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Lack of evidence of Metabolic Abnormalities and Mitochondrial Toxicity with Enfuvertide: a double-blind, placebo-controlled, cross-over study with random sequence assignation in healthy adult volunteers
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Reported by Jules Levin
9th Intl Workshopon Adverse Reactions and Lipodystrophy in HIV
July 19-21, 2007
Sydney, Australia
E Martinez et al. Hospital Clinic Barcelona, Spain
This study assessed the effects of the infusion inhibitor enfuvertide on lipid and carbohydrate metabolism and metabolism parameters in healthy adult volunteers.
Healthy normal-weight males aged 18-45 years without history of dislipemia or drug use had extensive blood cell and chemistry, urine history, serologies for HIV and hepatitis B and C, ECG, and screening for abuse drugs done at baseline and at the end of each period. Participants were randomized to enfuvertide 90 mg or placebo administered at hospital every 12 hours in two 7-day periods separated by a 4-week washout period. Major endpoint was total cholesterol (TC) change. Secondary endpoints were changes in HDL-C, LDL-C, triglycerides (TG), oral glucose tolerance test (OGTT), lactate, mtDNA and overall safety. The effects of period, treatment, and sequence (carry-over) were evaluated for each endpoint. Based on an expected interindividual variability <10 mg/dl of TC in healthy adults, a sample size of 12 persons would be needed to detect an increase >25 mg.dl in TC with 80% power and 0.025 one-sided alpha.
RESULTS
Of 17 persons recruited, 12 (6 enfuvertide + placebo, 6 placebo + enfuvertide) conmpleted the study. Baseline characteristics were similar in both groups. Lab variables were normally distributed. Mean +/- SD final/baseline TC and mean +/- TC )mg.dl) were: period 1, 0.93 +/-0.07 and 171 +/-45 (enfuvertide+placebo) and 0.91 +/-0.05 and 167 +/-38 (placebo+enfuvertide); period 2, 0.98 +/-0.05 and 180 +/-44 (enfuvertide+placebo) and 0.96 +/-0.10 and 174 +/-27 (placebo+enfuvertide; and considering the sequence enfuvertide+placebo, 0.96 +/-0.03 and 175 +/-44 and placebo + enfuvertide, 0.94 +/-0.04 and 170 +/-32 (p<0.4, each comparison). No patient showed an increase of >25 mg/dl in TC from baseline. Similarly, non-significant changes were also detected on considering HDL-C, LDL-C, TG, OGTT, and lactate. There were no effects of period, treatment, or sequence in lab endpoints other than mtDNA. A higher increase in final minus baseline mtDNA was associated with the second period. There were no remarkable clinical and lab adverse events.
Conclusion: The authors say "we were unable to detect any metabolic abnormalities or mitochondrial toxicity from use of enfuvertide in healthy adult volunteers.
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