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Trial · Interventional

CompletedPhase 2Results postedRegistry data

GPR119 Agonist for Hypoglycemia in Type 1 Diabetes

Short name PHROG

This trial does not test a peptide that PepBank tracks.

  • Measures Glucagon, does not give it. It appears in an outcome measure.

Overview

Status
Completed
Phase
Phase 2
Enrollment
110 participants (actual)
Sponsor
AdventHealth Translational Research Institute · Other
Design
Randomized · Double masking
Countries
1 country

United States

Start
21 Apr 2021
Primary completion
12 Aug 2023
Completion
12 Aug 2023
First posted
16 Jun 2020
Last update posted
17 Oct 2024
Conditions
Diabetes Mellitus, Type 1

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2021202220232024
  1. Ph 2

    PHROG

    NCT04432090

    21 Apr 2021 to 12 Aug 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The purpose of this study is to test if a specific research medication could increase the response to low blood glucose in people with type 1 diabetes. The response of the body to low blood sugar will be measured in healthy people as a reference point.

Interventions

  • PlaceboDrug
  • Study Medication (MBX-2982)Drug
  • No medication for this groupOther

Arms3

  • Experimental

    MBX-2982 first then placebo- Volunteers with Type 1 diabetes

    Participants with type 1 diabetes (T1D) will be randomized to either study medication or placebo group. In this arm, participants will receive a pill that contains the study medication (MBX-2982). This will be followed by a wash-out period and a cross over to the second study period in which they will receive a pill that does not contain the medication (placebo).

  • Active comparator

    Healthy Volunteers

    This group will not receive any medication. It will be studied to establish the norm of the measurement that will be performed to obtain the study outcomes.

  • Experimental

    Placebo first then MBX-2982- Volunteers with Type 1 diabetes

    Participants with type 1 diabetes (T1D) will be randomized to either study medication or placebo group. In this arm, participants will receive a pill that does not contain the medication (placebo). This will be followed by a wash-out period and a cross over to the second study period in which they will receive a pill that contains the study medication (MBX-2982).

Primary outcomes3

Outcomes the sponsor listed as primary.

  1. Maximal Glucagon Concentration During Hypoglycemia

    Time frame · Day 14, Day 42

    Registry description

    Maximal glucagon concentration during insulin induced hypoglycemia. This was measured during the hypoglycemic steady state of the hyper-insulinemic euglycemic-hypoglycemic clamp study.

  2. Total Area Under the Curve (AUC) for Glucagon During Hypoglycemia.

    Time frame · Day 14, Day 42

    Registry description

    This outcome was measured during the hypoglycemic steady state of the hyper-insulinemic euglycemic hypoglycemic clamp study. Total area under the curve (AUC) for glucagon was measured during the time points of 120 minutes to 140 minutes of the clamp.

  3. Incremental AUC for Glucagon During Hypoglycemia (Above Baseline Levels During Euglycemia)

    Time frame · Day 14, Day 42

    Registry description

    This is the difference between the AUC during the hypoglycemic steady state (time points 120 - 140 mins of clamp) and the baseline glucagon levels during euglycemic steady state (timepoints 60 min - 80 mins of the clamp)

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Day 14, Day 42

Maximal Glucagon Concentration During Hypoglycemia

GroupValue (pg/mL)Spread
T1D on MBX-298219.912.6
T1D on Placebo22.516.8
Healthy Normal Volunteers82.739.7
Primary outcomeMean· Day 14, Day 42

Total Area Under the Curve (AUC) for Glucagon During Hypoglycemia.

GroupValue (pg*min/mL)Spread
T1D on MBX-29826624.63772.4
T1D on Placebo6037.53545.9
Healthy Normal Volunteers15923.25350.6
Primary outcomeMean· Day 14, Day 42

Incremental AUC for Glucagon During Hypoglycemia (Above Baseline Levels During Euglycemia)

GroupValue (pg*min/mL)Spread
T1D on MBX-2982327.9257.9
T1D on Placebo467.8435.7
Healthy Normal Volunteers2445.41346.4

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
T1D on MBX-2982Participants with type 1 diabetes (T1D) who were randomized to the study drug, MBX-29820 / 180 / 184 / 18
T1D on PlaceboParticipants with type 1 diabetes (T1D) who were randomized to placebo0 / 180 / 185 / 18
Healthy Normal VolunteersParticipants enrolled in this group had no T1D and were not randomized to drug or placebo0 / 90 / 90 / 9

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 20 Years up to 60 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
INCLUSION CRITERIA Type 1 diabetes cohort: 1. Age 20-60 years 2. Diagnosis of T1DM according to American Diabetes Association (ADA) criteria continuously requiring insulin for survival 3. Diabetes diagnosis performed more than 5 years before enrollment 4. Fasting C-peptide levels \< 0.7 ng/mL with a concurrent plasma glucose concentration \> 90 mg/dL (Labs may need to be repeated if the Plasma glucose is \< 90 mg/dL) 5. For female participants: must be \> 6 months post-partum and not lactating and agrees not to become pregnant during the study and for at least 2 weeks after the last dose of the study medication. For male participants: agrees not to donate sperm or not to get a woman pregnant during the study and for at least 2 weeks after the last dose of the study medication. Healthy subject cohort: 1. Age 20-60 years 2. General good health 3. Creatinine clearance \>80 mL/min based on CKD-EPI equation 4. Fasting blood glucose (FBG) \>70 mg/dL and \<100 mg/dL 5. No history of diabetes 6. For female participants: must be \> 6 months post-partum and not lactating and agrees not to become pregnant during the study EXCLUSION CRITERIA: 1. BMI \>35 kg/m2 and \<18.5 kg/m2 for females and BMI \>35 kg/m2 and \<20 kg/m2 for males. 2. Increase or decrease body weight greater than 3kg in the 3 months before enrollment. 3. Evidence by history, ECG or exams of clinically significant cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, clinically significant abnormalities on ECG, presence of cardiac pacemaker, implanted cardiac defibrillator) 4. Evidence of autonomic neuropathy 5. Liver disease (AST or ALT \>2.5 times the upper limit of normal) 6. Kidney disease (creatinine \>1.6 mg/dl or estimated GFR \<60 ml/min). 7. Dyslipidemia, including triglycerides \>500 mg/dl, LDL \>200 mg/dl or unstable hyperlipidemia. Treatment with a single lipid lowering agents is allowed if stable within the previous 3 months. 8. Anemia (hemoglobin \<12 g/dl in men, \<11 g/dl in women) 9. Thyroid dysfunction (suppressed TSH, elevated TSH \<10 µIU/ml if symptomatic or elevated TSH \>10 µIU/ml if asymptomatic) 10. Uncontrolled hypertension (BP \>160 mmHg systolic or \>100 mmHg diastolic) or treatment with more than 2 antihypertensive medications. 11. Current use of beta-adrenergic blocking agents or their use was stopped less than one month before recruitment 12. History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable) 13. History of organ transplant 14. History of HIV, active Hepatitis B or C, or Tuberculosis 15. Pregnancy, lactation or 6 months postpartum from the scheduled date of screening lab collection 16. Females of childbearing potential (any female except those with tubal ligation, hysterectomy, or absence of menses \>2 years) unwilling to use an approved method of contraception (one medically accepted method of contraception with ≥99% effectiveness when used consistently and correctly). Male participants: he or he and his partner unwilling to use an approved method of contraception with ≥99% effectiveness when used consistently and correctly 17. History of Major Depression in the last 5 years 18. History of an eating disorder 19. History of bariatric surgery 20. History of drug or alcohol abuse (\> 3 drinks per day) within the last 5 years 21. Self-report of marijuana use ≥3 days/week in any form 22. Psychiatric disease prohibiting adherence to study protocol 23. Current use of oral or injectable anti-hyperglycemic agents: metformin, sulfonylureas, DPP IV inhibitors, SGLT-2 inhibitors, thiazolidinediones, acarbose, GLP-1 analogs 24. Initiation or change in hormone replacement therapy within the past 3 months (including, but not limited to thyroid hormone or estrogen replacement therapy). Hormone based contraception is acceptable. 25. Use of any medications known to influence glucose, fat and/or energy metabolism (e.g., growth hormone therapy, glucocorticoids \[steroids\], prescribed medications for weight loss, etc.). Patients on medications with acute effects on glucose metabolism used for other indications (certain antidepressants, ADHD and antiepileptic medications) may be enrolled if they have been on chronic, stable doses (≥6 months) 26. Uncontrolled seizure disorder 27. Current night shift worker 28. Presence of any condition that, in the opinion of the Investigator, compromises participant safety or data integrity or the participant's ability to complete study visits 29. Unwilling and/or unable to follow and comply with scheduled visits and protocol requirements Additional exclusion Criteria for the type 1 diabetes cohort: 1. HbA1c \>9% 2. Insulin dose less than 0.3 U/kg or low carbohydrate diet 3. History of T2DM or any form of diabetes other than T1DM 4. Hypoglycemia unawareness as assessed using the GOLD score 5. Using a predictive low blood glucose suspend mode on an insulin pump or a hybrid closed loop algorithm for insulin delivery. For those applying these strategies for everyday management of blood glucose and willing to participate, the algorithm will be stopped at enrollment. 6. Two or more episodes of severe hypoglycemia (Hypoglycemia requiring help from a third party) per month in the past six months 7. One or more DKA episodes in the past 3 months 8. QTcF \>450 msec for males and \>470 msec for females 9. Using non-insulin agents to control blood glucose levels 10. History or evidence of moderate or severe end-organ diabetic complications of retinopathy, nephropathy or neuropathy. Proliferative diabetic retinopathy. Non-proliferative retinopathy and microalbuminuria will be allowed. Additional exclusion Criteria for the healthy cohort: 1\. Insulin treatment

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