Relationship Between Gastric Emptying and Glycemic Variability in Type 1 Diabetes Mellitus

The study comprised 3 outpatient visits over a period of 11 days. Safety lab test were
performed at the screening visit. At each visit, GE was evaluated by 13C-spirulina breath
tests.

Phase 1:

After the baseline assessment (GE1), the second and third GE tests were performed during
treatment with intravenous (GE2) and oral erythromycin (GE3) or placebo. Subject arrived
fasting at each study visit. Prior to gastric emptying study, there was placement of an
intravenous line. Subject continued to take insulin and other medications as usual. Subjects
were required to do finger-stick glucose readings 4 times a day or as instructed by their
physician. Subjects were provided with a log sheet to keep track of meal times, insulin
dosing and times, glucose readings, and activities. Continuous glucose monitoring (CGM) and
gastric emptying were evaluated for the duration of the study (11 days) and thrice
respectively. GE was evaluated at baseline (GE1) and after randomized to intravenous saline,
erythromycin (2 mg/kg) or erythromycin (3 mg/kg).

Phase 2:

Thereafter, patients were randomized to erythromycin ethyl succinate suspension (250 mg tid)
or placebo for a total period of 7 days. GE3 was preferably performed on day 7, after oral
erythromycin or placebo was started.

An EKG was performed at baseline to identify (and exclude) patients who have
contraindications to erythromycin. An EKG was also repeated at the end of the study, i.e.,
on GE3 for safety. No change to insulin (apart from those that patients do with their self
management skills) or other medications was made during this research study.

Inclusion Criteria:

- Healthy male or non-pregnant non-breastfeeding female volunteers with type 1 diabetes
mellitus (T1 DM) undergoing a clinically-indicated continuous glucose monitoring
(CGM) study (Women of childbearing potential may be enrolled if they use
contraceptives throughout the length of the study).

- Able to provide written informed consent before participating in the study

- Able to communicate adequately with the investigator and to comply with the
requirements for the entire study.

- Glycated hemoglobin (A1c) < 8.5 %

Exclusion Criteria:

- Severe nausea or vomiting precluding study assessments

- Use of medications that alter GI motility e.g., narcotics, medications with
significant anticholinergic effects, CYP-450 3A4 inhibitors, antibiotics (other than
the experimental drug erythromycin), pramlintide or GLP-1 based therapy. Subjects
using metoclopramide or erythromycin will be enrolled but these medications will be
held for 7 days before CGM1 and GE1

- Pancreas transplantation

- Contraindications to erythromycin: i.e., 1) concomitant therapy with astemizole,
cisapride, pimozide, or terfenadine; 2) hypersensitivity to erythromycin or any
component of the product; Corrected QT interval on EKG >460 msec

- Known family history of sudden death or congenital QT prolongation

- Serum potassium and magnesium levels outside of normal range at screening or visit 1

- Patients with moderate or severe renal insufficiency, i.e., subjects with an eGFR <
60 mL/min/1.73 m^2)

- Patients who are allergic to eggs, wheat or milk or unwilling to consume these
products.