@article {117510,
	title = {A double-blind, placebo-controlled phase II study of the efficacy and safety of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease.},
	journal = {American journal of hematology},
	volume = {89},
	year = {2014},
	month = {2014 Jul},
	pages = {709-13},
	abstract = {<p>This placebo-controlled phase II study evaluated the pharmacodynamics, efficacy and safety of 2,2-dimethylbutyrate (HQK-1001), a fetal globin gene-inducing short-chain fatty acid derivative, administered orally at 15 mg/kg twice daily for 48 weeks in 76 subjects with sickle cell disease (SCD). The median age was 26 years (range: 12-55 years) and 37 subjects (49\%) were treated previously with hydroxycarbamide. Sixty subjects (79\%) had Hb SS and 16 (21\%) had S/β(0) thalassemia. The study was terminated after a planned interim analysis showed no significant increase in fetal hemoglobin (Hb F) and a trend for more pain crises in the HQK-1001 group. For 54 subjects with Week 24 data, the mean absolute increase in Hb F was 0.9\% (95\% confidence interval (CI): 0.1-1.6\%) with HQK-1001 and 0.2\% (95\% CI: -0.7-1.1\%) with placebo. Absolute increases in Hb F greater than 3\% were noted in 9 of 38 subjects (24\%) administered HQK-1001 and 1 of 38 subjects (3\%) administered placebo. The mean changes in hemoglobin at Week 24 were comparable between the two groups. The mean annualized rate of pain crises was 3.5 with HQK-1001 and 1.7 with placebo. The most common adverse events in the HQK-1001 group, usually graded as mild or moderate, consisted of nausea, headache, vomiting, abdominal pain, and fatigue. Additional studies of HQK-1001 at this dose and schedule are not recommended in SCD. Intermittent HQK-1001 administration, rather than a daily regimen, may be better tolerated and more effective, as shown previously with arginine butyrate, and warrants further evaluation.</p>
},
	keywords = {Administration, Oral, Adolescent, Adult, Anemia, Sickle Cell, Antisickling Agents, Butyrates, Child, Dose-Response Relationship, Drug, Double-Blind Method, Female, Fetal Hemoglobin, Humans, Male, Middle Aged, Placebos, Young Adult},
	issn = {1096-8652},
	doi = {10.1002/ajh.23725},
	author = {Reid, Marvin E and Amal ElBeshlawy and Inati, Adlette and Kutlar, Abdullah and Abboud, Miguel R and Haynes, Johnson and Ward, Richard and Sharon, Bruce and Taher, Ali T and Smith, Wally and Manwani, Deepa and Ghalie, Richard G}
}
