Pharmacodynamics and Pharmacokinetics of Different Glucose Bead Formulations in Obese Healthy Subjects

• Status: Completed
• Trial end date: 2020-11-09
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this clinical study was to assess pharmacodynamics (PD) and pharmacokinetics (PK) of different Glucose beads formulations in obese healthy subjects under fasting condition. The study was designed in 2 parts.

Part 1 (single-dose) of the study was randomized, open label, five-treatment, five-period, five-sequence, crossover and single-centric. Treatment arms were three dosages of a coated Glucose beads formulation (47% w/w glucose/bead; 8 g [T1], 12 g [T2] and 16 g glucose [T3]), one uncoated Glucose beads formulation (47% w/w glucose/bead; 12 g glucose [T4]) and one coated Glucose beads formulation (60% w/w glucose/bead;12 g glucose [T5]).

Part 2 (multiple-dose) of the study was open label, one-treatment, one-period and single-centric. Treatment arm was coated Glucose beads formulation (12 g glucose [T2]).

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Aphaia Pharma US LLC
• Collaborators: ACC GmbH Analytical Clinical Concepts; Galephar Pharmaceutical Research (PR), Inc.; NovaClin Medical Research Center S.R.L; SC Bioclinica SA

Criteria

Inclusion Criteria:

• Healthy obese, Caucasian, male and female subjects 18 - 55 years of age

• Body mass index within the range of > 30.0 kg/m2

• Waist circumference: men > 102 cm

• women > 88 cm

• Female subjects of childbearing potential agree to undergo pregnancy tests and to use an appropriate method of contraception (i.e. oral contraceptive steroids, intrauterine device, barrier method)

• Findings within the range of clinical acceptability in medical history (or the clinical investigator considers the deviation to be irrelevant for the purpose of the study)

• Findings within the range of clinical acceptability in physical examination (or the clinical investigator considers the deviation to be irrelevant for the purpose of the study)

• Laboratory values within the normal range (or the clinical investigator considers the deviation to be irrelevant for the purpose of the study)

• Normal ECG or abnormalities which the clinical investigator does not consider a disqualification for participation in the study

• Normal vital signs (normal blood pressure and heart rate measured under stabilised conditions at screening visit after at least 5 minutes of rest in sitting position) or abnormalities which the clinical investigator does not consider a disqualification for participation in the study

• Normal GI function, or abnormalities which the clinical investigator does not consider a disqualification for participation in the study

• Willingness to undergo screening and follow-up examinations (i.e. physical examinations and laboratory investigations before and after the treatment periods)

• Ability to comprehend subject information and willingness to sign the informed consent

Exclusion Criteria:

• Gastrointestinal, hepatic and renal diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the investigational product

• Established diagnosis of type-1 or type-2 diabetes mellitus

• Treatment with insulin, insulin secretagogues (sulfonylurea derivatives, glinides, GLP-1 agonists (exenatide, lixisenatide, glutides), or thiazolidinediones (glitazones)

• Unexplained rise in blood glucose

• Treatment for constipation (including but not limited to lactulose or any other form of stool softeners, laxatives) or diarrhea (including but not limited to pectins, loperamide etc.) or any other medication known to interfere with gastrointestinal transit time, such as e.g. metoclopramide, opioids, or gastric potential of hydrogen (pH) (including but not limited to antacids, H2-receptor antagonists, prazoles)

• History of hypersensitivity to the investigational product or any related drugs or to any of the excipients

• History or presence of any clinically significant cardiovascular, pulmonary, hepatobiliary, renal, hematological, gastrointestinal, endocrinologic, immunologic, dermatologic, neurological, psychiatric, metabolic, musculoskeletal, or malignant disease, which the clinical investigator does not consider a disqualification for participation in the study

• Known heart failure (Grade I to IV of New York Heart Association classification)

• Significant renal disease, including nephritic syndrome, chronic renal failure (defined as creatinine clearance < 60 mL/min and serum creatinine >180 μmol/L)

• Unexplained serum creatine phosphokinase (CPK) > 3-times the upper limit of normal (ULN).

• Subjects with a reason for CPK elevation may have the measurement repeated prior to randomization; a CPK retest > 3-times ULN leads to exclusion.

• Clinically significant abnormal laboratory values

• Clinically significant ECG findings

• Clinically significant vital signs

• Clinically significant illness or surgery within 4 weeks prior to dosing

• Less than 14 days after last acute disease

• Volunteers liable to orthostatic dysregulation, fainting, or blackouts

• History of, or current compulsive alcohol abuse (more than a total of 10 drinks weekly whereby one drink corresponds to 500 ml beer, 200 ml wine or 50 g spirits); or regular exposure to other substances of abuse

• Donation or loss of blood equal to or exceeding 500 ml during 90 days before the first administration of investigational product

• Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis C-virus (HCV)

• Participation in another study with an experimental drug within at least 3 months (or within five elimination half-lives of the previous experimental drug, whichever is longer) before the first administration of investigational product

• Any use of drug, prescribed or over the counter (OTC) (inclusive herbal remedies), within 2 weeks (or within six elimination half-lives of this medication, whichever is longer) prior to the first administration of investigational product except if this will not affect the outcome of the study in the opinion of the clinical investigator

• Pregnant women (positive pregnancy test)

• Lactating women

• Failure to provide informed consent

• Unwillingness or inability to comply with the study protocol or study-related procedures (e.g. difficulty to stay fasting, consume the standard meals, or swallow the beads formulations; difficult venous access)

• Positive result of rRT-PCR test to detect infection with the new SARS-CoV-2 coronavirus