A Clinical Study in Healthy Subjects Which Aims to Investigate the Safety, the Tolerability and the Effects of GRT0151Y and How the Compound is Taken up and Excreted From the Body

NCT ID: NCT03761407

Last Updated: 2018-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-30
• Study Completion Date: 2005-07-26

Brief Summary

The aim of this clinical study in healthy participants is to investigate the safety and tolerability of GRT0151Y after multiple oral intake of different increasing doses and to evaluate the pharmacological effects (action of the compound) by means of pupillometry (measuring the pupil size of the eye) and Cold Presser Test (measuring the pain when immersing the hand in 2 degree Celsius cold water). An additional aim of the study is to investigate the pharmacokinetics of GRT0151Y (how it is taken up into the body and how it is excreted from the body)."

Conditions

Acute Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1 (100 mg GRT0151Y)

The dose of 100 mg will be administered twice (b.i.d.) on Day 1 (titration day). On Days 2, 3 and 4, the treatment regimen will be changed to a triple daily (t.i.d) medication with 100 mg. On Day 5 the last dose of 100 mg will be administered in the morning.

Matching placebo using the same dosing regimen as defined in the treatment group.

Group Type: EXPERIMENTAL

100 mg GRT0151Y

Intervention Type: DRUG

100 mg capsule (1 x 100 mg capsule)

Matching placebo

Intervention Type: DRUG

Matching placebo capsules using the same dosing regimen as defined in the treatment groups.

Group 2 (125 mg GRT0151Y)

The dose of 125 mg will be administered twice (b.i.d.) on Day 1 (titration day). On Days 2, 3 and 4, the treatment regimen will be changed to a triple daily (t.i.d) medication with 125 mg. On Day 5 the last dose of 125 mg will be administered in the morning.

Matching placebo using the same dosing regimen as defined in the treatment group

Group Type: EXPERIMENTAL

125 mg GRT0151Y

Intervention Type: DRUG

125 mg (1 x 100 mg capsule and 1 x 25 mg capsule)

Matching placebo

Intervention Type: DRUG

Matching placebo capsules using the same dosing regimen as defined in the treatment groups.

Group 3 (150 mg GRT0151Y)

The dose of 150 mg will be administered twice (b.i.d.) on Day 1 (titration day). On Days 2, 3 and 4, the treatment regimen will be changed to a triple daily (t.i.d) medication with 150 mg. On Day 5 the last dose of 150 mg will be administered in the morning.

Matching placebo using the same dosing regimen as defined in the treatment group

Group Type: EXPERIMENTAL

150 mg GRT0151Y

Intervention Type: DRUG

150 mg (1 x 100 mg capsule and 1 x 50 mg capsule)

Matching placebo

Intervention Type: DRUG

Matching placebo capsules using the same dosing regimen as defined in the treatment groups.

Group 4 (225 mg GRT0151Y)

The dose of 150 mg will be administered twice (b.i.d.) on Day 1 (titration day). On Days 2, 3 and 4, the dose of 225 mg will be administered twice (b.i.d.). On Day 5 the last dose of 225 mg will be administered in the morning.

Matching placebo using the same dosing regimen as defined in the treatment group

Group Type: EXPERIMENTAL

225 mg GRT0151Y

Intervention Type: DRUG

Day 1: 150 mg (1 x 100 mg capsule and 1 x 50 mg capsule) Day 2 - 5: 225 mg (2 x 100 mg capsules and 1 x 25 mg capsule)

Matching placebo

Intervention Type: DRUG

Matching placebo capsules using the same dosing regimen as defined in the treatment groups.

Interventions

100 mg GRT0151Y

100 mg capsule (1 x 100 mg capsule)

Intervention Type: DRUG

125 mg GRT0151Y

125 mg (1 x 100 mg capsule and 1 x 25 mg capsule)

Intervention Type: DRUG

150 mg GRT0151Y

150 mg (1 x 100 mg capsule and 1 x 50 mg capsule)

Intervention Type: DRUG

225 mg GRT0151Y

Day 1: 150 mg (1 x 100 mg capsule and 1 x 50 mg capsule) Day 2 - 5: 225 mg (2 x 100 mg capsules and 1 x 25 mg capsule)

Intervention Type: DRUG

Matching placebo

Matching placebo capsules using the same dosing regimen as defined in the treatment groups.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female Caucasian.
• Age 40-65 years.
• Body mass index (BMI) between 18 and 30 kilograms/square meter (extremes included).
• Extensive Cytochrome P450 2D6 (CYP2D6) metabolizer.
• Healthy as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory parameters (haematology, Blood sedimentation rate (BSR), clotting, bio-chemistry, urinalysis and virus serology). Minor deviations of laboratory values and ECG parameters from the normal range may be accepted, if judged by the investigator as clinically not relevant and if not considered to interfere with the study objectives.
• Adequate contraception. For females of childbearing potential (i.e. all females except surgically sterilized or at least 2 years postmenopausal) this is defined as follows: any form of hormonal contraception or intra-uterine device must be used, at least for 4 weeks prior to the first dosing AND she must give a consent to use an additional barrier contraception (condom or diaphragm) from 2 weeks prior to first dosing up to 4 weeks after the last dosing.
• Written consent to participate in the study.
• Negative Human immunodeficiency virus (HIV)1/2-antibodies, Hepatitis B surface (HBs)-antigen, Hepatitis B core (HBc)-antibodies, Hepatitis C virus (HCV)-antibodies determined at screening examination.
• Negative drug abuse screening test determined at screening examination (the test will include screening for metamphetamine, opiate, cannabis, cocaine, amphetamine and benzodiazepine).
• Negative beta-human chorion gonadotropin test for females of childbearing potential determined at screening examination (the test is not necessary in females who are in post-menopausal state for at least 2 years or in females with status after surgical sterilisation).
• The participant must be able to tolerate the cold pressor test, i.e. he/she must be able to keep his/her hand for 120 seconds in cold water of about 2 degrees celsius.
• The participant must be able to undergo the procedure of pupillometry.

Exclusion Criteria

• Pulse rate below 45 or above 100 Beats per minute (bpm). The measurement must be performed in supine position after a resting period of at least 5 minutes.
• Systolic blood pressure below 100 or above 160 Millimeter mercury (mmHg), diastolic blood pressure below 50 or above 100 mmHg. The measurement must be performed in supine position after a resting period of at least 5 minutes.
• History or presence of diseases or functional disorders of the Central nervous system (CNS), endocrinological system, gastrointestinal tract, hepatobiliary system, renal system, respiratory system or cardiovascular system or other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs.
• Marked repolarisation abnormality (e.g. suspicious or definite congenital long QT syndrome) or co-medication that is known to influence cardiac repolarisation substantially.
• History of seizures or at risk (epilepsy in family anamnesis, unclear loss of consciousness), head trauma requiring hospitalization.
• Neurotic personality, psychiatric illness or suicide risk.
• History of orthostatic hypotension.
• Bronchial asthma.
• Definite or suspected history of drug allergy or hypersensitivity.
• History of Raynaud´s disease or phenomenon.
• Malignancy.
• Participation in another clinical study within three month prior to the start of this study (exception: characterization of metabolizer status).
• Blood donation (more than 100 Milliliter(s) or a comparable blood loss within three month prior to the start of this study.
• Excessive consumption of food or beverages containing caffeine or other xanthines (more than 1000 Milliliter(s) coffee or equivalent per day) within two weeks prior to the start of this study.
• Evidence of alcohol, medication or drug abuse.
• Smokers who are not able to abstain from smoking during the hospitalisation.
• Intake of drugs that are inhibitors of CYP2D6 isoenzyme within the last 4 weeks prior to the start of this study. Use of any other medication within two weeks prior to the start of the study (self-medication or prescription), if not on a stable basis and known to interfere with study objectives.
• Known or suspected of not being able to comply with the study protocol or of not being able to communicate meaningfully with the investigator and staff.
• Opinion of the investigator the volunteer should not participate in the study.
• Pregnant or breastfeeding.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Grünenthal GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Grünenthal Study Director

Role: STUDY_DIRECTOR

Grünenthal GmbH

Locations

ASTER

Paris, , France

Countries

France

Other Identifiers

HP0151Y/09

Identifier Type: -

Identifier Source: org_study_id