A Long-Term Extension Study of AT2101 (Afegostat Tartrate) in Type 1 Gaucher Patients

This was an open-label, long-term extension study of afegostat tartrate in participants with type 1 Gaucher disease who successfully completed Study GAU-CL-202 (NCT00446550). Participants could enter the study immediately upon completion of participation in the lead-in study GAU-CL-202, or at any later time point. Participants received 225 milligram (mg) afegostat tartrate, administered orally for 30 months, and remained in 1 of the 2 randomized treatment regimens of Study GAU-CL-202: afegostat tartrate once daily (QD) for 3 consecutive days, then no afegostat tartrate for 4 consecutive days (consecutive 3-days-on/4-days-off) or QD for 7 consecutive days, then no afegostat tartrate for 7 days (consecutive 7-days-on/7-days-off). Amendment 2 removed the 7-days-on/7-days-off regimen and added an alternative 3-days-on/4-days-off regimen: afegostat tartrate QD on Monday, Wednesday, and Friday, then no afegostat tartrate on Tuesday, Thursday, Saturday, and Sunday (MWF 3-days-on/4-days-off). Once Amendment 2 was implemented at a site, participants assigned to the 7-days-on/7-days-off regimen switched to a 3-days-on/4-days-off regimen; those on the original 3-days-on/4-days-off regimen could switch to the MWF 3-days-on/4-days-off regimen. Amendment 4 removed the original 3-days-on/4-days-off regimen and any participants still on that regimen switched to the MWF 3-days-on/4-days-off regimen. Study visits occurred every 3 months for 30 months. Participants were contacted approximately 1, 3, and 6 months after the end of treatment (EOT) or early termination for follow-up assessments.

Inclusion criteria

• Male or female participants, 18 years of age or older
• Completed study GAU-CL-202 with no significant protocol violations or safety concerns
• Clinically stable
• Had not received enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) in the past 12 months and was willing not to initiate ERT or SRT during study participation
• Agreed to practice an acceptable method of contraception
• Provided written informed consent to participate in the study

Exclusion criteria

• During the screening period, had any clinically significant findings which would compromise the safety of the participant, or preclude the participant from completing the study as deemed by the investigator
• Had a clinically significant disease, severe complications from Gaucher disease, or serious intercurrent illness that may preclude participation in the study, in the opinion of the Investigator
• Had a history of allergy or sensitivity to the study drug or any excipients, including any prior serious allergic reaction to iminosugars (for example, miglustat)
• Had a pacemaker or other contraindication for magnetic resonance imaging scanning
• Was pregnant or breast-feeding
• Had current gastrointestinal, liver, or kidney disease, sequelae of these diseases, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
• Participant was otherwise unsuitable for the study in the opinion of the Investigator