Clinical trial NCT03951987: Investigation How CG5503 is Taken up and Excreted From the Body After 2 Minutes Intravenous Infusion With and Without Oral Co-administration of Charcoal
Official title: Investigation of the Pharmacokinetic Properties of CG5503 After 2 Minutes Intravenous Infusion With and Without Oral Coadministration of Charcoal in a Randomised, Open, Single Dose, 2-way Crossover, Phase I Study in 12 Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetic
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
First posted: 2019-05-16
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The randomization was in the ratio 1:1.
Primary purpose: TREATMENT

Brief summary: This was a Phase I study in 12 healthy male participants to compare the pharmacokinetic properties of CG5503 (how it is taken up and excreted from the body) after 2 minutes intravenous (i.v.) infusion with and without oral co-administration of charcoal to investigate a potential gastrointestinal secretion of CG5503.

During the course of the study each participant received two infusions of 40 mg CG5503 without (treatment A) and with (treatment B) oral co-administration of charcoal. In treatment B, eight doses of 5 grams charcoal powder were co-administered orally at defined time points. The wash out phases were to be at least 4 to 14 days between the treatment periods.


Eligibility criteria: Inclusion Criteria:

* Male Caucasian participants aged 18 - 65 years.
* Body mass index (BMI) between 20 and 30 kilograms/square meter inclusive.
* Participants must be in good health as determined by medical history, physical examination, 12-lead electrocardiogram, vital signs, and clinical laboratory parameters (serum/urine biochemistry, serology and haematology). Minor deviations of laboratory values from the normal range may be accepted, if judged by the investigator to have no clinical relevance and if not considered to interfere with the study objectives.
* Negative human immunodeficiency virus (HIV)-1/-2 antibodies, hepatitis B surface (HBs)-antigen, hepatitis B core (HBc)-antibodies, hepatitis C virus (HCV)-antibodies at the screening examination.
* Participants giving written consent to participate within this trial.

Exclusion Criteria:

* Use of any medication within four weeks prior to commencement of the study (self-medication or prescription), if not on a stable basis.
* Diseases and functional disorders of the gastrointestinal tract, liver, cardiovascular system or kidneys.
* Malignancy.
* History of orthostatic hypotension.
* Resting pulse rate equal to or below 45 beats/min or equal to or above 100 beats/min.
* Systolic blood pressure equal to or below 100 mmHg or equal to or above 160 mmHg.
* Diastolic blood pressure equal to or below 50 mmHg or equal to or above 95 mmHg.
* Clinically relevant deviations in laboratory parameters.
* Drug allergy.
* Bronchial asthma.
* Participation in another clinical study in the last three months before starting this study (exception: characterization of metabolizer status).
* Blood donation (more than 100 milliliter) in the last three months before the start of the study.
* Evidence of alcohol or drug abuse.
* Positive drug abuse screening test.
* Extremely unbalanced diet (in the opinion of the investigator).
* Excessive consumption of food or beverages containing caffeine (more than five cups of coffee per day or other equivalent amounts of caffeine).
* Consumption of grapefruit juice two weeks before the start of the study.
* Known or suspected of not being able to comply with the study protocol.
* Not able to communicate meaningfully with the investigator and staff.
* Neurotic personality, psychiatric illness, or suicide risk.
* History of seizures or at risk (i.e. head trauma, epilepsy in family anamnesis, unclear loss of consciousness).

Primary outcomes:
measure: Pharmacokinetic parameter Serum: area under the concentration-time curve extrapolated to infinity (AUC0-inf) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Saliva: area under the concentration-time curve extrapolated to infinity (AUC0-inf) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: area under the concentration-time curve extrapolated to infinity (AUC0-inf) for CG5503-glucuronide
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: area under the concentration-time curve extrapolated to infinity (AUC0-inf) for CG5503-sulphate
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: area under the concentration-time curve from 0 to time t (AUC0-t) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Saliva: area under the concentration-time curve from 0 to time t (AUC0-t) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: area under the concentration-time curve from 0 to time t (AUC0-t) for CG5503-glucuronide
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: area under the concentration-time curve from 0 to time t (AUC0-t) for CG5503-sulphate
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: maximum concentration (Cmax) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Saliva: maximum concentration (Cmax) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: maximum concentration (Cmax) for CG5503-glucuronide
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: maximum concentration (Cmax) for CG5503-sulphate
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: time to maximum concentration (tmax) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Saliva: time to maximum concentration (tmax) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: time to maximum concentration (tmax) for CG5503-glucuronide
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: time to maximum concentration (tmax) for CG5503-sulphate
timeFrame: Pre-dose and up to 23 hours post-dose
Secondary outcomes:
measure: Pharmacokinetic parameter Serum: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Saliva: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for CG5503-glucuronide
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for CG5503-sulphate
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: apparent terminal elimination rate constant (λz) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Saliva: apparent terminal elimination rate constant (λz) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: apparent terminal elimination rate constant (λz) for CG5503-glucuronide
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: apparent terminal elimination rate constant (λz) for CG5503-sulphate
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: the apparent half-life associated with the terminal elimination phase (t1/2,z) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Saliva: the apparent half-life associated with the terminal elimination phase (t1/2,z) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: the apparent half-life associated with the terminal elimination phase (t1/2,z) for CG5503-glucuronide
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: the apparent half-life associated with the terminal elimination phase (t1/2,z) for CG5503-sulphate
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: total serum or blood clearance of drug after intravenous administration (CL) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Saliva: total clearance of drug after intravenous administration (CL) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: total serum or blood clearance of drug after intravenous administration (CL) for CG5503-glucuronide
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: total serum or blood clearance of drug after intravenous administration (CL) for CG5503-sulphate
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: the apparent volume of distribution associated with terminal phase after intravenous administration (Vz) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Saliva: the apparent volume of distribution associated with terminal phase after intravenous administration (Vz) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: the apparent volume of distribution associated with terminal phase after intravenous administration (Vz) for CG5503-glucuronide
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Serum: the apparent volume of distribution associated with terminal phase after intravenous administration (Vz) for CG5503-sulphate
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Urine: renal excretion (Ae % of dose) for CG5503 base
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Urine: renal excretion (Ae % of dose) for CG5503-glucuronide
timeFrame: Pre-dose and up to 23 hours post-dose
measure: Pharmacokinetic parameter Urine: renal excretion (Ae % of dose) for CG5503-sulphate
timeFrame: Pre-dose and up to 23 hours post-dose
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Department of Clinical Pharmacology Grünenthal GmbH
Study officials:
affiliation: Grünenthal GmbH
name: Grünenthal Study Director
role: STUDY_DIRECTOR
References: