Pharmacodynamics and Pharmacokinetics of 3 New Developed Coated Glucose Beads in 20 Obese Healthy Subjects

Pharmacodynamics and Pharmacokinetics of 3 New Developed Coated Glucose Beads Formulations After Single-dose Administration (Fasting Conditions) in 20 Obese Healthy Subjects

This single-dose, randomized, open label, five-treatment, five-period, five-sequence crossover study was performed to assess pharmacodynamics (PD) and pharmacokinetics (PK) of three new developed coated Glucose beads formulations (containing glucose (8 g) and caffeine), one coated Glucose beads formulation (containing glucose (8 g)) and one uncoated Glucose beads formulation (containing Glucose (8 g) and caffeine) after single-dose administration (fasting conditions) in 20 obese healthy subjects. After an overnight fasting of at least 10 hours the subjects were administered either glucose (8 g) or glucose (8 g) and caffeine starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position. At least 3 days wash-out period was kept between each treatment periods.

Study Overview

• Status: Completed
• Conditions: Obesity; Metabolic Syndrome
• Intervention / Treatment: Drug: coated beads glucose (8 g) and caffeine anhydrous; Drug: coated beads glucose (8 g); Drug: uncoated beads glucose (8 g) and caffeine anhydrous

Detailed Description

This single-dose, randomized, open label, five-treatment, five-period, five-sequence crossover study was performed to assess pharmacodynamics (PD) and pharmacokinetics (PK) of three new developed coated Glucose beads formulations (containing glucose (8 g) and caffeine), one coated Glucose beads formulation (containing glucose (8 g)) and one uncoated Glucose beads formulation (containing Glucose (8 g) and caffeine) after single-dose administration (fasting conditions) in 20 obese healthy subjects.

Only subjects who had given voluntarily their informed consent participated in the screening examination and, if found eligible as per study inclusion and exclusion criteria, were enrolled in the study. At least 13 hours before investigational product administration in each treatment period, subjects were admitted to the clinical site. During each treatment period the hospitalization period in the clinical unit was 13 hours before and up to 11 hours after investigational product administration.

Test products (T1, T 2, T3, T4, T5) was administered as single oral doses during the first, second, third, fourth and fifth treatment period corresponding to the randomization code under fasting conditions.

After an overnight fasting of at least 10 hours, the subjects were administered either glucose (8 g) or glucose (8 g) and caffeine starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position. According to the randomization code subjects were received on the respective study day one coated beads formulations (T1, T2, T3, T 4) or the uncoated beads formulation (T5).

A total of 17 blood samples were drawn for determination of Glucagon-like peptide-1 (GLP-1) levels and pharmacokinetic analysis of caffeine at the prescribed times, pre-dose (1.0 h, 0.5 hand 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration. Blood samples for glucose measurements was taken via an indwelling catheter or vein puncture from the forearm vein pre-dose (1.0 h, and 0 h) and at 0.5, 1.0, 2.0, 3.0, 4 0, 5.0, 6 0, 8.0 and 10.0 hours after investigational product administration.

Visual analogue scale (VAS) (appetite), VAS (stomach rumbles) were evaluated at the prescribed times pre-dose (0 h) and at 2, 4 and 10 hours after investigational product administration.

Wash-out periods of at least 3 days were separated the five treatment periods.

Within 7 days after last blood sampling in the last treatment period 12-lead electrocardiogram (ECG), vital signs, clinical routine laboratory parameters, physical examination and check of adverse events were repeated.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Romania
  • Timisoara, Romania, 300696
    • Nova-Clin Medical Research Center S.R.L.,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 stabilized 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 gastrointestinal (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
• Non-smokers or mild to moderate smokers (less or equal 10 cigarettes daily)

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, prazole)
• Tea, coffee or other caffeine containing beverage drinkers (more than 0.4 L per day)
• 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 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
• Donation or loss of blood equal to or exceeding 500 ml during 90 days before the first administration of investigational product
• 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
• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Test product 1 (T1); Aphaia Pharma (APH)-001A: glucose coated beads containing 8 g glucose and caffeine anhydrous	Drug: coated beads glucose (8 g) and caffeine anhydrous; After an overnight fasting of about 10 hours the subjects were administered either glucose (8 g) or glucose (8 g) and caffeine starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position on Day 1.; Other Names: APH-001C
ACTIVE_COMPARATOR: Test product 2 (T2); APH-001B: glucose coated beads containing 8 g glucose and caffeine anhydrous	Drug: coated beads glucose (8 g) and caffeine anhydrous; After an overnight fasting of about 10 hours the subjects were administered either glucose (8 g) or glucose (8 g) and caffeine starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position on Day 1.; Other Names: APH-001C
ACTIVE_COMPARATOR: Test product 3 (T3); APH-001C: glucose coated beads containing 8 g glucose and caffeine anhydrous	Drug: coated beads glucose (8 g) and caffeine anhydrous; After an overnight fasting of about 10 hours the subjects were administered either glucose (8 g) or glucose (8 g) and caffeine starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position on Day 1.; Other Names: APH-001C
ACTIVE_COMPARATOR: Test product 4 (T4); APH-001D: glucose coated beads containing 8 g glucose	Drug: coated beads glucose (8 g); After an overnight fasting of about 10 hours the subjects were administered glucose (8 g) starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position on Day 1.; Other Names: APH-001D
ACTIVE_COMPARATOR: Test product 5 (T5); APH-001E: uncoated beads containing 8 g glucose and caffeine anhydrous	Drug: uncoated beads glucose (8 g) and caffeine anhydrous; After an overnight fasting of about 10 hours the subjects were administered either glucose (8 g) or glucose (8 g) and caffeine starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position on Day 1.; Other Names: APH-001E

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GLP-1	Area under the plasma concentration-time curve (AUC(0-t))	Pre-dose (-1.0 h, -0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
GLP-1	AUC(1.5h-6h)	Pre-dose (-1.0 h, -0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
GLP-1	Adjusted area under the plasma concentration-time cur (AUCadj(1.5h-6h))	Pre-dose (-1.0 h, -0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
GLP-1	Maximum plasma concentration (Cmax(0-t))	Pre-dose (-1.0 h, -0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
GLP-1	Cmax(1.5h-6h)	Pre-dose (-1.0 h, -0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
GLP-1	Cmax,adj(1.5h-6h)	Pre-dose (-1.0 h, -0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
GLP-1	time to reach maximum plasma concentration (tmax(0-t))	Pre-dose (-1.0 h, -0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
GLP-1	tmax(1.5h-6h)	Pre-dose (-1.0 h, -0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
GLP-1	Duration of time during the concentration in the plasma concentration-time curve exceeds at least 50 % of Cmax(1.5h-6h)	Pre-dose (-1.0 h, -0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of Caffeine	AUC(0-t)	Pre-dose (1.0 h, 0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
Pharmacokinetics of Caffeine	Cmax(0-t)	Pre-dose (1.0 h, 0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
Pharmacokinetics of Caffeine	tmax(0-t)	Pre-dose (1.0 h, 0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
Pharmacokinetics of Caffeine	tlag	Pre-dose (1.0 h, 0.5 h and 0 h) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration
Pharmacokinetics of Glucose	AUC(0-t)	Venous blood glucose measurement at the prescribed times pre-dose (-1.0 h, 0 h) and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0 and 10.0 hours after investigational product administration
Pharmacokinetics of Glucose	Cmax(0-t)	Venous blood glucose measurement at the prescribed times pre-dose (-1.0 h, 0 h) and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0 and 10.0 hours after investigational product administration
Pharmacokinetics of Glucose	tmax(0-t)	Venous blood glucose measurement at the prescribed times pre-dose (-1.0 h, 0 h) and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0 and 10.0 hours after investigational product administration
Visual analogue scale (VAS) appetite	VAS for appetite with score of 1 - 10 was measured	VAS (appetite) at the prescribed times pre-dose (0 h) and 2, 4 and 10 hours after investigational product administration.
VAS stomach rumbles	VAS for stomach rumbles with score of 1 - 10 was measured	VAS (stomach rumbles) at the prescribed times pre-dose (0 h) and 2, 4 and 10 hours after investigational product administration.
Tolerability and safety	12-lead ECG	Within 7 days after last blood sampling in the last treatment period
Tolerability and safety	vital signs	Within 7 days after last blood sampling in the last treatment period
Tolerability and safety	clinical routine laboratory parameters	Within 7 days after last blood sampling in the last treatment period
Tolerability and safety	physical examination	Within 7 days after last blood sampling in the last treatment period
Tolerability and safety	check of adverse events	Within 7 days after last blood sampling in the last treatment period

Collaborators and Investigators

• Sponsor: Aphaia Pharma US LLC
• Collaborators: BioClinica, Inc.; ACC GmbH Analytical Clinical Concepts, Germany; Nova-Clin Medical Research Center S.R.L., Romania; Galephar Pharmaceutical Research (PR), Inc, Puerto Rico
• Investigators: Principal Investigator: Carmen Vizman, Doctor, Aphaia Pharma AG

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 25, 2019
• Primary Completion (ACTUAL): December 3, 2019
• Study Completion (ACTUAL): December 3, 2019

Study Registration Dates

• First Submitted: January 19, 2023
• First Submitted That Met QC Criteria: January 27, 2023
• First Posted (ACTUAL): February 6, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: January 27, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine
• Other Study ID Numbers: 017B19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No