Sardh E.1, Rejkjaer L.2, Harper P.3, Andersson D.E.H.1
1Dept of Internal Medicine, South General Hospital, Stockholm, Sweden, 2HemeBiotech A/S, Hillerød, Denmark, 3Porphyria Centre Sweden, Huddinge University Hospital, Stockholm, Sweden
The study was a combined phase I and II study with the primary objective to study the safety and tolerability of a single and repeated dose(s) of i.v. rhPBGD and the pharmacokinetics of a single and repeated dose(s) of i.v. rhPBGD. The secondary objectives were to study the biochemical efficacy by measuring the change in plasma concentration of PBG over time for both single and repeated dose(s) of rhPBGD. The trial was an open label, dose escalating, rhPBGD single dose (Part A), and a double blind, randomised, placebo controlled repeated dose (Part B) study. There were 4 doses (0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg) and Part A of the trial involved 12 AIP subjects with 3 subjects at each dose level. Part B involved 20 healthy AIP subjects and 20 healthy male (non-AIP) subjects with 10 subjects at each dose level, one AIP subject and one healthy male (non-AIP) were randomized to placebo at each dose level. The results of this trial showed that rhPBGD seem to have biphasic pharmacokinetic characteristics. The terminal half-life was about 2.5 hours. Approximate dose proportionality was observed.. The i.v. bolus injection of rhPBGD produced an instant, almost complete, removal of plasma PBG lasting for at least 2 hours even at the lowest dose of 0.25 mg/kg bid. After 2 hours, the plasma PBG level increased gradually at slower rates for higher doses and the initial level is reached after 12 hours. No reduction was produced by placebo. No safety issues were raised during the trial and rhPBGD was well tolerated.