@article {117514,
	title = {A dose-escalation phase IIa study of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease.},
	journal = {American journal of hematology},
	volume = {88},
	year = {2013},
	month = {2013 Nov},
	pages = {E255-60},
	abstract = {<p>2,2-Dimethylbutyrate (HQK-1001), an orally-bioavailable promoter-targeted fetal globin gene-inducing agent, was evaluated in an open-label, randomized dose-escalation study in 52 subjects with hemoglobin SS or S/β(0) thalassemia. HQK-1001 was administered daily for 26 weeks at 30 mg/kg (n = 15), 40 mg/kg (n = 18) and 50 mg/kg (n = 19), either alone (n = 21) or with hydroxyurea (n = 31). The most common drug-related adverse events were usually mild or moderate and reversible. Gastritis was graded as severe in three subjects at 40 mg/kg and was considered the dose-limiting toxicity. Subsequently all subjects were switched to the maximum tolerated dose of 30 mg/kg. Due to early discontinuations for blood transfusions, adverse events or non-compliance, only 25 subjects (48\%) completed the study. Drug plasma concentrations were sustained above targeted levels at 30 mg/kg. Increases in fetal hemoglobin (Hb F) were observed in 42 subjects (80\%), and 12 (23\%) had increases >=4\%. The mean increase in Hb F was 2\% [95\% confidence interval (CI), 0.8-3.2\%] in 21 subjects receiving HQK-1001 alone and 2.7\% (95\% CI, 1.7-3.8\%) in 31 subjects receiving HQK-1001 plus hydroxyurea. Total hemoglobin increased by a mean of 0.65 g/dL (95\% CI, 0.5-1.0 g/dL), and 13 subjects (25\%) had increases >=1 g/dL. Future studies are warranted to evaluate the therapeutic potential of HQK-1001 in sickle cell disease. .</p>
},
	keywords = {Administration, Oral, Adolescent, Adult, Anemia, Sickle Cell, Antisickling Agents, beta-Thalassemia, Butyrates, Child, Cohort Studies, Dose-Response Relationship, Drug, Female, Fetal Hemoglobin, Gastritis, Hematinics, Heterozygote, Humans, Hydroxyurea, Incidence, Male, Middle Aged, Patient Dropouts, Promoter Regions, Genetic, Sickle Cell Trait, Up-Regulation, Young Adult},
	issn = {1096-8652},
	doi = {10.1002/ajh.23533},
	author = {Kutlar, Abdullah and Reid, Marvin E and Inati, Adlette and Taher, Ali T and Abboud, Miguel R and Amal El-Beshlawy and Buchanan, George R and Smith, Hedy and Ataga, Kenneth I and Perrine, Susan P and Ghalie, Richard G}
}
