Galanello 1999.

Methods	2‐period, randomised, double‐blind, placebo‐controlled, sequential parallel‐group design.
Participants	25 people with transfusion‐dependent β‐thalassaemia were randomised Age (mean (SD)): 21.6 (3.3) years Gender (male/female): 25/0 Setting and country: 2 centers in Italy Country: Italy Inclusion criteria: White males Age ≥ 18 years Transfusion‐dependent β‐thalassaemia Participants had serum ferritin values between ≥ 1500 ng/mL and ≤ 5000 ng/mL, as well as post‐transfusion haemoglobin levels of at least 13 ± 0.5 g/ dL All patients had previously been treated with a mean daily dose of 20 to 50 mg/kg/day DFO for at least 4 weeks before screening. Exclusion criteria: History of systemic reactions to treatment with DFO History of systemic disease Any medical condition that might have significantly altered the absorption, distribution, metabolism, or excretion of the study drug Follow‐up: safety: Up to 10 days post dose
Interventions	"Following a 16‐day run‐in period, 24 patients were allocated to one of three study groups, with each group consisting of 8 patients. Each group was administered two single oral doses of ICL670 at an interval of at least 7 weeks, first a lower dose and later a higher dose. Group 1 received 2.5 and 20 mg/kg, group 2 received 5 and 40 mg/kg, and group 3 received 10 and 80 mg/kg ICL670, in all cases given as an oral suspension of 100 mL prepared from dispersible tablets. Before proceeding to a higher dose, the safety and tolerability of the preceding dose had to be assessed as satisfactory. In each treatment period, 2 of 8 patients received placebo in such a way that a given patient did not receive placebo more than once. Patients went back to their usual deferoxamine therapy and transfusion scheme in the interval between study periods."
Outcomes	Urinary iron excretion Serum iron Transferrin Safety assessment: physical examination, vital signs, ECG, audiometry, clinical laboratory evaluations, and AE monitoring. Safety laboratory evaluations: hematology (including transferrin and serum iron), biochemistry (including routine renal and liver function parameters, zinc, copper, and vitamin C), special kidney function parameters (α‐glutathione‐S‐transferase, N‐acetyl‐β‐Dglucosaminidase, β2‐microglobulin, and retinol‐binding protein), urinalysis
Notes	Novartis involved in trial. No details given and no information available with regard to potential conflicts of interest.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details given with regard to sequence generation. From information given in paper, unclear, whether randomisation took place both in group assignment and in allocating patients to placebo. Author confirmed that randomisation was used to allocate placebo. "Randomization was used to assign both drug (all treatment groups) and placebo. Hope to have clarified."
Allocation concealment (selection bias)	Unclear risk	No details given with regards to concealment of allocation.
Blinding (performance bias and detection bias) All outcomes	Low risk	"The study employed a two‐period, randomised, double‐blind, placebo‐controlled, sequential parallel group design." However, no definition of double‐blind. Unclear whether, e.g. outcome assessors and data analysts were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Not applicable. Data from all participants are presented.
Selective reporting (reporting bias)	Unclear risk	Only general information with regard to safety issues. No clear‐cut comparison of placebo vs verum groups. Unclear, whether other parameters were evaluated than those reported.
Other bias	Low risk	No other risk of bias detected.