Trial Outcomes & Findings for Bromocriptine Quick Release (BCQR) as Adjunct Therapy in Type 1 Diabetes (NCT NCT02544321)

NCT ID: NCT02544321

Last Updated: 2021-09-13

Results Overview

At the end of each 4 week intervention period, we will measure the effect of Bromocriptine Quick Release on average glucose levels (mg/dl) by continuous glucose monitoring

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 108 participants
• Primary outcome timeframe: 4 weeks
• Results posted on: 2021-09-13

Participant Flow

Some participants screen failed or withdrew from the study after enrollment, but prior to starting the study.

Participant milestones

Measure	Bromocriptine QR, Then Placebo 4 weeks of investigational drug Bromocriptine QR, then 4 weeks of placebo.	Placebo, Then Bromocriptine QR 4 weeks of placebo, then 4 weeks of investigational drug Bromocriptine QR
Overall Study STARTED	43	43
Overall Study Completed First Treatment	43	41
Overall Study Completed Washout	43	41
Overall Study Started Second Treatment	42	40
Overall Study COMPLETED	41	39
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Measure	Bromocriptine QR, Then Placebo 4 weeks of investigational drug Bromocriptine QR, then 4 weeks of placebo.	Placebo, Then Bromocriptine QR 4 weeks of placebo, then 4 weeks of investigational drug Bromocriptine QR
Overall Study Withdrawal by Subject	1	2
Overall Study Adverse Event	1	1
Overall Study Protocol Violation	0	1

Baseline Characteristics

Adults and adolescents are divided by rows

Baseline characteristics by cohort

Measure	Bromocriptine QR, Then Placebo n=43 Participants 4 weeks of investigational drug Bromocriptine QR, then 4 weeks of placebo.	Placebo, Then Bromocriptine QR n=41 Participants 4 weeks of placebo, then 4 weeks of investigational drug Bromocriptine QR	Total n=84 Participants Total of all reporting groups
Race (NIH/OMB) Adolescents · Asian	0 Participants n=22 Participants • Adults and adolescents are divided by rows	0 Participants n=20 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Age, Continuous Adults	44.1 years STANDARD_DEVIATION 9.0 • n=21 Participants • Adults and adolescents are divided by rows	38 years STANDARD_DEVIATION 10.0 • n=21 Participants • Adults and adolescents are divided by rows	41.1 years STANDARD_DEVIATION 9.9 • n=42 Participants • Adults and adolescents are divided by rows
Age, Continuous Adolescents	16.5 years STANDARD_DEVIATION 2.8 • n=22 Participants • Adults and adolescents are divided by rows	15.6 years STANDARD_DEVIATION 2.7 • n=20 Participants • Adults and adolescents are divided by rows	16.1 years STANDARD_DEVIATION 2.8 • n=42 Participants • Adults and adolescents are divided by rows
Sex: Female, Male Adults · Female	12 Participants n=21 Participants • Adults and adolescents are divided by rows	11 Participants n=21 Participants • Adults and adolescents are divided by rows	23 Participants n=42 Participants • Adults and adolescents are divided by rows
Sex: Female, Male Adults · Male	9 Participants n=21 Participants • Adults and adolescents are divided by rows	10 Participants n=21 Participants • Adults and adolescents are divided by rows	19 Participants n=42 Participants • Adults and adolescents are divided by rows
Sex: Female, Male Adolescents · Female	15 Participants n=22 Participants • Adults and adolescents are divided by rows	9 Participants n=20 Participants • Adults and adolescents are divided by rows	24 Participants n=42 Participants • Adults and adolescents are divided by rows
Sex: Female, Male Adolescents · Male	7 Participants n=22 Participants • Adults and adolescents are divided by rows	11 Participants n=20 Participants • Adults and adolescents are divided by rows	18 Participants n=42 Participants • Adults and adolescents are divided by rows
Ethnicity (NIH/OMB) Adults · Hispanic or Latino	0 Participants n=21 Participants • Adults and adolescents are divided by rows	1 Participants n=21 Participants • Adults and adolescents are divided by rows	1 Participants n=42 Participants • Adults and adolescents are divided by rows
Ethnicity (NIH/OMB) Adults · Not Hispanic or Latino	21 Participants n=21 Participants • Adults and adolescents are divided by rows	20 Participants n=21 Participants • Adults and adolescents are divided by rows	41 Participants n=42 Participants • Adults and adolescents are divided by rows
Ethnicity (NIH/OMB) Adults · Unknown or Not Reported	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Ethnicity (NIH/OMB) Adolescents · Hispanic or Latino	1 Participants n=22 Participants • Adults and adolescents are divided by rows	2 Participants n=20 Participants • Adults and adolescents are divided by rows	3 Participants n=42 Participants • Adults and adolescents are divided by rows
Ethnicity (NIH/OMB) Adolescents · Not Hispanic or Latino	21 Participants n=22 Participants • Adults and adolescents are divided by rows	18 Participants n=20 Participants • Adults and adolescents are divided by rows	39 Participants n=42 Participants • Adults and adolescents are divided by rows
Ethnicity (NIH/OMB) Adolescents · Unknown or Not Reported	0 Participants n=22 Participants • Adults and adolescents are divided by rows	0 Participants n=20 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adults · American Indian or Alaska Native	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adults · Asian	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adults · Native Hawaiian or Other Pacific Islander	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adults · Black or African American	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adults · White	21 Participants n=21 Participants • Adults and adolescents are divided by rows	21 Participants n=21 Participants • Adults and adolescents are divided by rows	42 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adults · More than one race	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adults · Unknown or Not Reported	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=21 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adolescents · American Indian or Alaska Native	0 Participants n=22 Participants • Adults and adolescents are divided by rows	0 Participants n=20 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adolescents · Native Hawaiian or Other Pacific Islander	0 Participants n=22 Participants • Adults and adolescents are divided by rows	0 Participants n=20 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adolescents · Black or African American	0 Participants n=22 Participants • Adults and adolescents are divided by rows	1 Participants n=20 Participants • Adults and adolescents are divided by rows	1 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adolescents · White	22 Participants n=22 Participants • Adults and adolescents are divided by rows	19 Participants n=20 Participants • Adults and adolescents are divided by rows	41 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adolescents · More than one race	0 Participants n=22 Participants • Adults and adolescents are divided by rows	0 Participants n=20 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Race (NIH/OMB) Adolescents · Unknown or Not Reported	0 Participants n=22 Participants • Adults and adolescents are divided by rows	0 Participants n=20 Participants • Adults and adolescents are divided by rows	0 Participants n=42 Participants • Adults and adolescents are divided by rows
Region of Enrollment United States	43 participants n=43 Participants	41 participants n=41 Participants	84 participants n=84 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: Data reflects average glucose levels.

At the end of each 4 week intervention period, we will measure the effect of Bromocriptine Quick Release on average glucose levels (mg/dl) by continuous glucose monitoring

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=40 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=40 Participants 4 weeks of placebo Placebo
Mean Glucose	182 mg/dl Standard Error 5	165 mg/dl Standard Error 5	181 mg/dl Standard Error 5	165 mg/dl Standard Error 5

PRIMARY outcome

Timeframe: 4 weeks

At the end of each 4 week intervention period, we will measure the effect of BCQR on insulin dosing (units//kg/day)

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=40 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=40 Participants 4 weeks of placebo Placebo
Insulin Dosing	0.9 units//kg/day Standard Error .03	0.54 units//kg/day Standard Error .02	0.88 units//kg/day Standard Error .03	0.56 units//kg/day Standard Error 0.02

PRIMARY outcome

Timeframe: 4 weeks

Population: Compared for placebo versus BCQR after 4 weeks of treatment.

At the end of each 4 week intervention period, we will measure the brachial artery distensibility as a measure of vascular stiffness by Dynapulse (%/mmHg). A larger number indicates less stiffness (ie greater compliance).

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=40 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=40 Participants 4 weeks of placebo Placebo
Brachial Artery Distensibility	6.35 %/mmHg Standard Error 0.19	6.2 %/mmHg Standard Error 0.2	6.14 %/mmHg Standard Error 0.19	6.4 %/mmHg Standard Error 0.2

PRIMARY outcome

Timeframe: 4 weeks

At the end of each 4 week intervention period, we will measure the reactive hyperemia Index (RHI). The Reactive Hyperemia Index (RHI) measures increased bloodflow after vascular occlusion. Higher scores indicate lower CVD risk and a better outcome, Scores of less than 1.67 may be considered abnormal. Scores of 1.67 1.67-2.09 may be considered borderline, and scores of 2.10 or higher my be considered normal.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=40 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=40 Participants 4 weeks of placebo Placebo
Hyperemia Peripheral Arterial Tonometry (RH-PAT): Reactive Hyperemia Index (RHI)	1.95 score on a scale Standard Error 0.09	2.1 score on a scale Standard Error 0.1	2.24 score on a scale Standard Error 0.09	2.2 score on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: 4 weeks

At the end of each 4 week intervention period, we will measure the effect of Bromocriptine Quick Release on glycemic variability throughout the day (mg/dl), measured as SD of all glucose values throughout the last 7 days of intervention. Incorrectly initially entered as primary outcome. per protocol this has always been a secondary outcome.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=40 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=40 Participants 4 weeks of placebo Placebo
Mean Glycemic Variability	71 mg/dl Standard Error 2.1	61 mg/dl Standard Error 2.5	73 mg/dl Standard Error 2.1	63 mg/dl Standard Error 2.5

SECONDARY outcome

Timeframe: 4 weeks

Population: Unadjusted least square means by mixed procedure.

At the end of each 4 week intervention period, we will measure Hypoglycemia Awareness using the Gold method (7 point Likert scale: Possible scores range from 1 to 7. higher scores indicate more impaired awareness of hypoglycemia, and a worse outcome), Clarke method (8 question questionnaire characterizing hypoglycemia awareness. Possible scores range from 0-7, with higher scores indicating less awareness and a worse outcome), and the McAuley score (list of symptoms with a 7 point Likert scale for each. Possible scores range from 1-7 for each item, and are averaged across all symptoms, for a total possible score range of 1-7, with higher scores indicating more symptom awareness, and a better outcome).

Incorrectly initially entered as primary outcome. per protocol this has always been a secondary outcome.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=41 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=41 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=41 Participants 4 weeks of placebo Placebo
Hypoglycemia Awareness Gold method scores	2.15 score on a scale Standard Error 1.31	3.02 score on a scale Standard Error 1.67	2.00 score on a scale Standard Error 1.18	3.15 score on a scale Standard Error 1.59
Hypoglycemia Awareness Clarke method scores	1.36 score on a scale Standard Error 1.23	2.33 score on a scale Standard Error 1.90	1.33 score on a scale Standard Error 1.20	2.67 score on a scale Standard Error 1.84
Hypoglycemia Awareness McAuley score	3.25 score on a scale Standard Error 0.22	3.40 score on a scale Standard Error 0.31	3.21 score on a scale Standard Error 0.22	2.90 score on a scale Standard Error 0.29

SECONDARY outcome

Timeframe: 4 weeks

At the end of each 4 week intervention period, the % will be measured by SyphgmoCor. The Augmentation Index measures vascular stiffness by comparing pulse pressure of the reflected wave to the primary wave. HIGHER scores indicate greater vascular stiffness and higher cardiovascular risk, but a normal range has not been clearly defined. Presented as AI normalized to a heart rate of 75 (AI75).

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=40 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=40 Participants 4 weeks of placebo Placebo
Augmentation Index	10.42 Percentage of pressure wave Standard Error 1.71	-2.0 Percentage of pressure wave Standard Error 1.8	12.52 Percentage of pressure wave Standard Error 1.72	-2.5 Percentage of pressure wave Standard Error 1.8

SECONDARY outcome

Timeframe: 4 weeks

At the end of each 4 week intervention period we will measure the autonomic function by ECG. Ratio of maximum heart rate/minimum heartrate during a valsalva maneuver.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) 4 weeks of placebo Placebo	Placebo (Adults) 4 weeks of placebo Placebo
Heart Rate Variability (Adults)	1.09 ratio Standard Error 0.05	1.14 ratio Standard Error 0.05	—	—

SECONDARY outcome

Timeframe: 4 weeks

At the end of each 4 week intervention period we will measure the autonomic function by HRV measured by endopat and reported using the single gold standard measure of SDNN (standard deviation of beat to beat time interval). Normal is >100, 50-100 indicates compromised autonomic function.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=40 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) 4 weeks of placebo Placebo	Placebo (Adults) 4 weeks of placebo Placebo
Heart Rate Variability (Adolescents)	73 milliseconds Standard Error 5	76.4 milliseconds Standard Error 4.9	—	—

SECONDARY outcome

Timeframe: 4 weeks

At the end of each 4 week intervention period, measurements of sleep duration on weekdays and weekends (minutes) by a Philips Spectrum Plus sleep monitor will be obtained.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=42 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=42 Participants 4 weeks of placebo Placebo
Sleep Duration weekdays	433 minutes Standard Deviation 69	394 minutes Standard Deviation 59	414 minutes Standard Deviation 47	402 minutes Standard Deviation 62
Sleep Duration weekends	486 minutes Standard Deviation 81	458 minutes Standard Deviation 95	464 minutes Standard Deviation 85	453 minutes Standard Deviation 98

SECONDARY outcome

Timeframe: 4 weeks

At the end of each 4 week intervention period, measurements of sleep efficiency (percent of time in bed spent asleep) during the week and on weekends by a Philips Spectrum Plus sleep monitor will be obtained.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=42 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=42 Participants 4 weeks of placebo Placebo
Sleep Quality efficiency during the week	87.9 percent Standard Deviation 5.3	90.4 percent Standard Deviation 4.2	89.0 percent Standard Deviation 4.1	90.4 percent Standard Deviation 4.4
Sleep Quality efficiency weekends	88.3 percent Standard Deviation 4.8	89.7 percent Standard Deviation 5.0	89.0 percent Standard Deviation 5.4	90.9 percent Standard Deviation 3.6

SECONDARY outcome

Timeframe: 4 weeks

Population: glucose and triglyceride total AUC least square means +/- SD

At the end of each 4 week intervention period, glucose, insulin, triglycerides, NEFA, GLP-1, and glucagon area under the curve will be measured during Mixed Meal Tolerance Test.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=42 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=42 Participants 4 weeks of placebo Placebo
Metabolic Markers-glucose and Triglycerides Glucose	11735 mg*hr/dL Standard Deviation 7180	9228 mg*hr/dL Standard Deviation 5530	11356 mg*hr/dL Standard Deviation 5990	12357 mg*hr/dL Standard Deviation 6962
Metabolic Markers-glucose and Triglycerides Triglycerides	3452 mg*hr/dL Standard Deviation 2878	3445 mg*hr/dL Standard Deviation 4582	3066 mg*hr/dL Standard Deviation 2040	3460 mg*hr/dL Standard Deviation 4634

SECONDARY outcome

Timeframe: 4 weeks

Population: Non-esterified fatty acids total AUC least square means +/- SD

At the end of each 4 week intervention period, glucose, insulin, triglycerides, NEFA, GLP-1, and glucagon area under the curve will be measured during Mixed Meal Tolerance Test.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=42 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=42 Participants 4 weeks of placebo Placebo
Metabolic Markers-fatty Acids	123334 microEq*hr/L Standard Deviation 115005	75561 microEq*hr/L Standard Deviation 52616	93661 microEq*hr/L Standard Deviation 58385	67497 microEq*hr/L Standard Deviation 46017

SECONDARY outcome

Timeframe: 4 weeks

Population: glucagon total AUC least square means +/- SE

At the end of each 4 week intervention period, glucose, insulin, triglycerides, NEFA, GLP-1, and glucagon area under the curve will be measured during Mixed Meal Tolerance Test.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=42 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=42 Participants 4 weeks of placebo Placebo
Metabolic Markers-glucagon	2398 pg*hr/mL Standard Deviation 1959	2160 pg*hr/mL Standard Deviation 1361	2011 pg*hr/mL Standard Deviation 1252	2350 pg*hr/mL Standard Deviation 1491

SECONDARY outcome

Timeframe: 4 weeks

Population: GLP-1 total AUC least square means +/- SD

At the end of each 4 week intervention period, glucose, insulin, triglycerides, NEFA, GLP-1, and glucagon area under the curve will be measured during Mixed Meal Tolerance Test.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=42 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=42 Participants 4 weeks of placebo Placebo
Metabolic Markers - GLP1	661 pmol*hr/L Standard Deviation 435	872 pmol*hr/L Standard Deviation 563	766 pmol*hr/L Standard Deviation 392	1196 pmol*hr/L Standard Deviation 728

SECONDARY outcome

Timeframe: 4 weeks

Population: insulin total AUC least square means +/- SD

At the end of each 4 week intervention period, glucose, insulin, triglycerides, NEFA, GLP-1, and glucagon area under the curve will be measured during Mixed Meal Tolerance Test.

Outcome measures

Measure	Bromocriptine QR (Adolescents) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=42 Participants 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=42 Participants 4 weeks of placebo Placebo	Placebo (Adults) n=42 Participants 4 weeks of placebo Placebo
Metabolic Markers - Insulin	4162 microIU*hr/mL Standard Deviation 2496	2386 microIU*hr/mL Standard Deviation 1087	4001 microIU*hr/mL Standard Deviation 3209	2379 microIU*hr/mL Standard Deviation 1160

Adverse Events

Bromocriptine QR (Adolescents)

Serious events: 1 serious events

Other events: 13 other events

Deaths: 1 deaths

Bromocriptine QR (Adults)

Serious events: 1 serious events

Other events: 17 other events

Deaths: 1 deaths

Placebo (Adolescents)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo (Adults)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bromocriptine QR (Adolescents) n=42 participants at risk 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=42 participants at risk 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=42 participants at risk 4 weeks of placebo Placebo	Placebo (Adults) n=42 participants at risk 4 weeks of placebo Placebo
Endocrine disorders severe hypoglycemia	2.4% 1/42 • Number of events 1 • 6 months	0.00% 0/42 • 6 months	0.00% 0/42 • 6 months	0.00% 0/42 • 6 months
Musculoskeletal and connective tissue disorders diagnosed with RA	0.00% 0/42 • 6 months	2.4% 1/42 • Number of events 1 • 6 months	0.00% 0/42 • 6 months	0.00% 0/42 • 6 months

Other adverse events

Measure	Bromocriptine QR (Adolescents) n=42 participants at risk 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Bromocriptine QR (Adults) n=42 participants at risk 4 weeks of investigational drug Bromocriptine QR Bromocriptine	Placebo (Adolescents) n=42 participants at risk 4 weeks of placebo Placebo	Placebo (Adults) n=42 participants at risk 4 weeks of placebo Placebo
Gastrointestinal disorders nausea	31.0% 13/42 • 6 months	40.5% 17/42 • 6 months	2.4% 1/42 • 6 months	7.1% 3/42 • 6 months
Vascular disorders orthostasis	9.5% 4/42 • 6 months	14.3% 6/42 • 6 months	0.00% 0/42 • 6 months	4.8% 2/42 • 6 months
General disorders fatigue	2.4% 1/42 • 6 months	11.9% 5/42 • 6 months	0.00% 0/42 • 6 months	7.1% 3/42 • 6 months
General disorders headache	4.8% 2/42 • 6 months	4.8% 2/42 • 6 months	2.4% 1/42 • 6 months	2.4% 1/42 • 6 months

Additional Information

Irene Schauer, MD

University of Colorado Denver

Phone: 3037241111

Email: clinicalresearchsupportcenter@ucdenver.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place