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Phase 2 N=49 Randomized Quadruple-blind Treatment

Study of MEDI0382 in Combination With Dapagliflozin and Metformin in Overweight/Obese Participants With Type 2 Diabetes

Type 2 Diabetes Mellitus

Enrolled (actual)
49
Serious AEs
0.0%
Results posted
Jan 2020
Primary outcome: Primary: Change From Baseline to Day 28 in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4hrs) as Measured by Mixed-meal Tolerance Test (MMTT) — -11.28; -154.37 hr·mg/dL — p=<0.0001

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
MEDI0382 (Drug); Placebo (Drug); Dapaglifozin (Drug); Metformin (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
MedImmune LLC
Primary completion
Dec 2018

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline to Day 28 in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4hrs) as Measured by Mixed-meal Tolerance Test (MMTT)
-11.28; -154.37 <0.0001 sig
PRIMARY
Percent Change From Baseline to Day 28 in Plasma Glucose AUC0-4hrs as Measured by MMTT
-0.13; -22.30 <0.0001 sig
SECONDARY
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
14; 13; 0; 0
SECONDARY
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Reported as TEAEs
0; 0
SECONDARY
Number of Participants With Abnormal Vital Signs Reported as TEAEs
2; 1; 1; 0; 0; 1
SECONDARY
Number of Participants With Abnormal Physical Examinations Reported as TEAEs
0; 0
SECONDARY
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
1; 0
SECONDARY
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC [0-∞]) of MEDI0382
106.4; 196.7; 314.6
SECONDARY
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC [0-∞]) of Dapagliflozin
432.6; 473.8; 410.2; 438.0; 421.0; 448.6
SECONDARY
Area Under the Plasma Concentration-time Curve During the Dosing Period (AUCtau) of MEDI0382
89.6; 165.0; 265.9
SECONDARY
Area Under the Plasma Concentration-time Curve During the Dosing Period (AUCtau) of Dapagliflozin
400.9; 430.3; 377.5; 406.8; 417.1; 396.8
SECONDARY
Maximum Observed Serum Concentration (Cmax) of MEDI0382
5.2; 10.1; 17.2
SECONDARY
Maximum Observed Serum Concentration (Cmax) of Dapagliflozin
110.1; 116.7; 92.0; 84.4; 95.6; 61.1
SECONDARY
Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI0382
5.5; 5.1; 4
SECONDARY
Time to Reach Maximum Observed Serum Concentration (Tmax) of Dapagliflozin
1; 1; 1; 1; 1.1; 1
SECONDARY
Terminal Elimination Half-life (t½) of MEDI0382
8.8; 9; 9.1
SECONDARY
Terminal Elimination Half-life (t½) of Dapagliflozin
8.2; 7.8; 7.9; 8.3; 7.0; 8.5
SECONDARY
Apparent Clearance (CL/F) of MEDI0382
1.1; 1.3; 1.2
SECONDARY
Apparent Clearance (CL/F) of Dapagliflozin
25.5; 23.3; 26.7; 25.7; 25.9; 25.5
SECONDARY
Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI0382
0; 3; 0; 1; 1; 2
SECONDARY
Change From Baseline in Plasma Glucose AUC24-hrs to the End of Each Dosing Level as Measured by Continuous Glucose Monitoring (CGM)
49.14; -832.66; 57.30; -666.05; 229.47; -726.85
SECONDARY
Change From Baseline in Mean 24-hrs Plasma Glucose to the End of Each Dosing Level as Measured by CGM
2.59; -34.74; 2.83; -28.34; 9.70; -30.55
SECONDARY
Change From Baseline in Standard Deviation of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM
-3.01; -7.21; 1.38; -7.52; -4.39; -9.76
SECONDARY
Change From Baseline in Coefficient of Variation of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM
-2.37; -0.45; 0.96; -2.06; -4.26; -3.21
SECONDARY
Change From Baseline in Mean Amplitude of Glucose Excursions (MAGE) of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM
-13.46; -25.74; 18.05; -26.59; -8.09; -27.92
SECONDARY
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Euglycemic Range to the End of Each Dosing as Measured by CGM
-5.61; 7.12; -2.79; 5.31; -4.17; 6.54
SECONDARY
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Hyperglycemic Range to the End of Each Dosing as Measured by CGM
3.62; -13.99; 0.36; -9.81; 6.08; -9.72
SECONDARY
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Hypoglycemic Range to the End of Each Dosing as Measured by CGM
1.17; 6.08; 2.00; 3.44; -2.08; 2.84
SECONDARY
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within Clinically Significant Hypoglycemic Range to the End of Each Dosing as Measured by CGM
0.76; 1.61; 0.27; -0.06; -0.26; 0.93

Summary

A Phase 2 study Comparing the effects on glucose control of MEDI0382 in combination with Dapagliflozin and Metformin compared to placebo in combination with Dapagliflozin and Metformin in overweight/obese participants with Type 2 Diabetes Mellitus (T2DM).

Eligibility Criteria

Inclusion Criteria

  • Male and female participants aged >= 18 years at screening.
  • Provision of signed and dated informed consent form (ICF) prior to any study specific procedures.
  • Body mass index between 25 kg/m^2 and 40 kg/m^2 (inclusive) at screening.
  • Hemoglobin A1c range between 7.0% and 10.0% (inclusive) at the time of screening.
  • Diagnosed with T2DM and treated with of metformin monotherapy (MTD > 1 g) at least 8 weeks prior to screening or treated with stable, oral doses of dapagliflozin 10 mg and metformin (MTD > 1 g) for at least 3 months prior screening.
  • Participants prescribed oral dual therapy with sulphonylurea, glitinide, or dipeptidyl peptidase-4 inhibitor (in addition to metformin) may be eligible to enter the study following a washout period of these medications totaling at least 28 days before initial screening evaluations have been completed.
  • Participants treated with stable doses of metformin (MTD > 1 g) with canagliflozin (maximum dose of 300 mg/day), or metformin (MTD > 1 g) with empaglifozin (maximum dose of 25mg/day) for at least 3 months prior to screening may be eligible to enter the study after switching to dapagliflozin.
  • Female participants of childbearing potential must have a negative pregnancy test at screening and randomization and must not be lactating.
  • Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from screening and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female participant to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

Exclusion Criteria

  • History of, or any existing condition that in the opinion of the investigator would interfere with evaluation of the investigational product, put the participant at risk, influence the participant's ability to participate, or affect the interpretation of the results of the study and/or any participant unable or unwilling to follow study procedures.
  • Any participant who has received another investigational product not included in the protocol as part of a clinical trial or a glucagon-like peptide-1 (GLP-1) analogue or sodium-glucose cotransporter-2 (SGLT2)-containing preparation (excluding dapagliflozin, canagliflozin, empagliflozin) within the last 30 days or 5 half-lives of the drug (whichever is longest) at the time of screening.
  • Any participant who has received any of the following medications prior to the start of the screening period (Visit 1) or prior to the study start period (Visit 4):
  • Concurrent use of any medicinal products, or herbal or over-the-counter (OTC) preparations licensed for control of body weight or appetite at the time of screening (Visit 1)
  • Concurrent or previous use of drugs approved for weight loss (eg, orlistat, bupropion-naltrexone, phentermine-topiramate, phentermine, lorcaserin) within the last 30 days or 5 half-lives of the drug (whichever is longest) at the time of screening (Visit 1)
  • Concurrent use of aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily and within the last 72 hours prior to the start of the study (Visit 4)
  • Concurrent use of paracetamol (acetaminophen) or paracetamol-containing preparations at a total daily dose of greater than 3000 mg and within the last 72 hours prior to the start of the study (Visit 4)
  • Concurrent use of ascorbic acid (vitamin C) supplements at a total daily dose greater than 1000 mg and within the last 72 hours prior to the start of the study (Visit 4)
  • Concurrent use of opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying and within the last 72 hours prior to the start of the stu
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03444584). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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