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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05713773
• Other study ID #: 017B19
• Status: Completed
• Phase: Phase 1
• Start date: October 25, 2019
• Est. completion date: December 3, 2019

Study information

• Verified date: January 2023
• Source: Aphaia Pharma US LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 3, 2019
• Est. primary completion date: December 3, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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).

Related Conditions & MeSH terms

• Metabolic Syndrome
• Obesity

Intervention

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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Romania	Nova-Clin Medical Research Center S.R.L.,	Timisoara

Sponsors (5)

Lead Sponsor	Collaborator
Aphaia Pharma US LLC	ACC GmbH Analytical Clinical Concepts, Germany, BioClinica, Inc., Galephar Pharmaceutical Research (PR), Inc, Puerto Rico, Nova-Clin Medical Research Center S.R.L., Romania

Country where clinical trial is conducted

Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	Tolerability and safety	12-lead ECG	Within 7 days after last blood sampling in the last treatment period
Secondary	Tolerability and safety	vital signs	Within 7 days after last blood sampling in the last treatment period
Secondary	Tolerability and safety	clinical routine laboratory parameters	Within 7 days after last blood sampling in the last treatment period
Secondary	Tolerability and safety	physical examination	Within 7 days after last blood sampling in the last treatment period
Secondary	Tolerability and safety	check of adverse events	Within 7 days after last blood sampling in the last treatment period