Investigation How CG5503 is Taken up and Excreted From the Body After 2 Minutes Intravenous Infusion With and Without Oral Co-administration of Charcoal

NCT03951987 | Completed Phase 1

• 1 other identifier: HP5503/11
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetic

Outcome Measures

Primary Outcomes (16)

• Pharmacokinetic parameter Serum: area under the concentration-time curve extrapolated to infinity (AUC0-inf) for CG5503 base

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-inf was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Saliva: area under the concentration-time curve extrapolated to infinity (AUC0-inf) for CG5503 base

  16 PK saliva samples were obtained from each participant. Saliva concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Participants were asked to donate saliva as much as possible in approximately 0.5 minutes. The AUC0-inf was calculated based on saliva concentration-time data (using the actual saliva sampling time intervals).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: area under the concentration-time curve extrapolated to infinity (AUC0-inf) for CG5503-glucuronide

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-inf was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: area under the concentration-time curve extrapolated to infinity (AUC0-inf) for CG5503-sulphate

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-inf was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: area under the concentration-time curve from 0 to time t (AUC0-t) for CG5503 base

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-t was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Saliva: area under the concentration-time curve from 0 to time t (AUC0-t) for CG5503 base

  16 PK saliva samples were obtained from each participant. Saliva concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Participants were asked to donate saliva as much as possible in approximately 0.5 minutes. The AUC0-t was calculated based on saliva concentration-time data (using the actual saliva sampling time intervals).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: area under the concentration-time curve from 0 to time t (AUC0-t) for CG5503-glucuronide

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-t was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: area under the concentration-time curve from 0 to time t (AUC0-t) for CG5503-sulphate

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-t was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: maximum concentration (Cmax) for CG5503 base

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Cmax was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Saliva: maximum concentration (Cmax) for CG5503 base

  16 PK saliva samples were obtained from each participant. Saliva concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Participants were asked to donate saliva as much as possible in approximately 0.5 minutes. tubes. The Cmax was calculated based on saliva concentration-time data (using the actual saliva sampling time intervals).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: maximum concentration (Cmax) for CG5503-glucuronide

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Cmax was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: maximum concentration (Cmax) for CG5503-sulphate

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Cmax was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: time to maximum concentration (tmax) for CG5503 base

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The tmax was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Saliva: time to maximum concentration (tmax) for CG5503 base

  16 PK saliva samples were obtained from each participant. Saliva concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Participants were asked to donate saliva as much as possible in approximately 0.5 minutes. The tmax was calculated based on saliva concentration-time data (using the actual saliva sampling time intervals).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: time to maximum concentration (tmax) for CG5503-glucuronide

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The tmax was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: time to maximum concentration (tmax) for CG5503-sulphate

  26 PK blood samples were obtained from each participant. Serum concentrations were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The tmax was calculated based on serum concentration-time data (using the actual blood sampling times).

  Pre-dose and up to 23 hours post-dose

Secondary Outcomes (23)

• Pharmacokinetic parameter Serum: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for CG5503 base

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Saliva: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for CG5503 base

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for CG5503-glucuronide

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for CG5503-sulphate

  Pre-dose and up to 23 hours post-dose

• Pharmacokinetic parameter Serum: apparent terminal elimination rate constant (λz) for CG5503 base

  Pre-dose and up to 23 hours post-dose

Study Arms (2)

Treatment A: 4 ml CG5503

EXPERIMENTAL

4 ml of the CG5503 i.v. infusion solution corresponding to 40 mg CG5503 (tapentadol hydrochloride) was administered as a 2 minutes infusion.

Drug: 4 ml CG5503

Treatment B: 4 ml CG5503; 5 g charcoal powder

EXPERIMENTAL

4 ml of the CG5503 i.v. infusion solution corresponding to 40 mg CG5503 (tapentadol hydrochloride) with oral co-administration of charcoal (5 g charcoal were co-administered orally at 1, 0.5 hours and 10 minutes before the start of CG5503 infusion and 0.5, 1, 1.5, 2 and 4 hours thereafter)

Drug: 4 ml CG5503; Drug: 5 g charcoal powder

Interventions

4 ml CG5503 DRUG

4 ml of the CG5503 infusion solution corresponding to 40 mg CG5503 (tapentadol hydrochloride).

Treatment A: 4 ml CG5503; Treatment B: 4 ml CG5503; 5 g charcoal powder

5 g charcoal powder DRUG

Oral administration of 5 g charcoal powder suspended in 100 ml tap water.

Also known as: Tradename: Kohle-Pulvis Pulver

Treatment B: 4 ml CG5503; 5 g charcoal powder

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (1)

Department of Clinical Pharmacology Grünenthal GmbH

Aachen, 52099, Germany

Location

MeSH Terms

Interventions

Tapentadol

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The randomization was in the ratio 1:1.

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 16, 2019
• Study Start: February 1, 2004
• Primary Completion: April 1, 2004
• Study Completion: April 1, 2004
• Last Updated: May 16, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)