Randomized, open-label preference study of two cyclosporine capsule formulations (usp modified) in stable solid-organ transplant recipients.
BACKGROUND
Prior research has indicated patient dissatisfaction with the odor, size, and taste of cyclosporine capsules, as well as the halitosis and body odor the capsules can cause.


OBJECTIVE
The purposes of this investigation were to (1) compare the overall cyclosporine capsule preference (Gengraf vs Neoral) in stable, solid-organ transplant recipients, (2) assess patient preference based on specific capsule attributes, and (3) determine the reliability of the Cyclosporine Capsule SatiSfaCtion Survey (original to this study).


METHODS
In this multicenter, randomized, open-label, parallel-group, preference study, patients were recruited from 144 centers in North America with established transplant programs. Solid-organ transplant recipients who had taken stable doses of cyclosporine (Neoral) for >/=2 consecutive months were randomized in a 9:1 ratio to receive another cyclosporine formulation (Gengraf) or to remain on Neoral therapy. Patients completed the Cyclosporine Capsule Satisfaction Survey prior to randomization (baseline survey) and after taking the study drug for 4 weeks (final survey). The survey consisted of multiple attribute items with high face validity in assessing patients' perceptions and preferences with regard to their overall experience, as well as specific attributes of cyclosporine capsules known to affect patient acceptance.


RESULTS
The intent-to-treat population included 1906 patients (1211 men, 693 women [sex unknown in 2 patients]; mean [SD] age, 50.2 [12.4] years). A total of 1708 patients were switched to Gengraf; 198 continued on Neoral. Based on their overall experience with both capsule formulations, the majority of patients switched to Gengraf (61.9%) responded that they preferred the Gengraf capsule, compared with 13.7% who preferred the Neoral capsule and 24.4% who indicated no preference (P < 0.001). A similar preference for Gengraf was observed based on capsule odor (66.3%), ease of swallowing (51.5%), taste (57.1%), and impact on breath odor (52.5%) and body odor (48.4%) (P < 0.001 for each test). The results of internal consistency and reproducibility calculations were high for the Cyclosporine Capsule Satisfaction Survey. Internal consistency ranged from alpha = 0.84 to 0.95 for the subscales and was alpha = 0.95 for the overall score. Ranges for reproducibility in the subscales were r = 0.75 to 0.79, with an overall reproducibility of r = 0.85. Guyatt's responsiveness statistics for the subscale and overall scores were moderately high to very high, indicating that the survey is capable of measuring change in response to treatment.


CONCLUSIONS
Of the transplant recipients receiving Gengraf in this study, most preferred Gengraf to Neoral based on overall experience, capsule odor, difficulty swallowing, taste, breath odor, and body odor. Among all study patients, fewer patients receiving Gengraf were bothered by capsule odor, difficulty in swallowing, taste, or the impact on breath or body odor compared with patients who continued to receive Neoral. Internal consistency, reproducibility, and responsiveness results show that the Cyclosporine Capsule Satisfaction Survey is a psychometrically valid instrument that is appropriate for use in clinical trials.
Steinberg
Steven M
SM
Kidney-Pancreas Transplant Program, Sharp Memorial Hospital, San Diego, California 93123, USA. sstein1@san.rr.com
Venuto
Rocco C
RC
Kuruvila
Chakko K
CK
Taylor
David O
DO
Anil Kumar
Mysore S
MS
Groothuis
Jessie R
JR
Ryan
Joan
J
Greco
Renee
R
Yeldandi
Vijay
V
Ashraf
Talat
T
Boodhoo
Terry
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002214:Capsules; D016572:Cyclosporine / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D017060:Patient Satisfaction; D011795:Surveys and Questionnaires
D002214:Capsules; D007166:Immunosuppressive Agents; D016572:Cyclosporine