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Clinical InvestigationsCYSTIC LUNG DISEASEA Phase I Trial of Intranasal Moli1901 for Cystic Fibrosis
Section snippets
Study Design
This was a phase I trial that was randomized, placebo controlled, and single blind to the participant. The study protocol was approved by the Johns Hopkins University School of Medicine Joint Committee on Clinical Investigation (institutional review board) and the Johns Hopkins General Clinical Research Center, and was performed in the Johns Hopkins Hospital Outpatient General Clinical Research Center. Participants gave informed consent.
Participant Characteristics
Healthy, non-CF participants 18 to 40 years of age were
Subjects
Four non-CF (one woman and three men) and four CF participants (three women and one man) enrolled and completed the study. One CF subject presented at screening with an elevated serum glucose level that was subsequently evaluated and treated.
Safety
No adverse events related to Moli1901 occurred during this study. There was no change in FEV1 after exposure to Moli1901 in either group. All eight subjects had no statistically significant change in any safety parameter after exposure to Moli1901.
All
NPD in Non-CF and CF Participants
Baseline assessments and postdose assessments were obtained for all subjects for both control and drug-treated nostrils. Follow-up NPD measurements without Moli1901 were repeated weekly for at least a month and until the responses were within 20% of baseline to assess duration of drug effect.
The baseline NPD, amiloride-sensitive response, chloride-free response, and isoproterenol response for normal and CF participants prior to drug exposure (Table 1) were compared. These data show that the
Discussion
The respiratory epithelium lining the inferior turbinate resembles structurally and functionally the epithelium lining the upper airways and can be used as a surrogate region for evaluating compounds that modulate airway epithelial ion transport.9 NPD measurements of basal or resting potential difference reflect the dominant sodium flux from lumen to submucosal space.1011 The contribution of sodium absorption to this potential difference is estimated by superfusing with amiloride to inhibit
Conclusions
In conclusion, Moli1901 was safe and well tolerated in nasal epithelium exposed to a concentration of up to 10 μmol/L. Chloride secretion was induced at 1 μmol/L, 3 μmol/L, and 10 μM in normal volunteers. CF participants also generated chloride secretion in response to Moli1901 at 3 μM, but more variability was observed. Further, these studies justify the conduct of a pilot efficacy study of Moli1901 in CF.
ACKNOWLEDGMENT
The authors thank Ms. Lois Brass-Ernst and Ms. Terry Williams for the execution of this clinical trial.
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This work was supported in part by SBIR grant 1 R43HL57070-01A1, The North Carolina Biotechnology Center, NIH/NCRR grant RR-00052 at The Johns Hopkins University General Clinical Research Center, Molichem Medicines, Inc., and the Cystic Fibrosis Foundation.