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

NCT03761407 | Completed Phase 1

• 1 other identifier: HP0151Y/09
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events.

  Number of adverse events and number of participants with adverse events.

  From the first IMP administration (Day 1) to the Final Examination (Day 4 to 11 after last period).

Secondary Outcomes (22)

• Pupillometry parameter: Initial pupil diameter

  Day 1 at 0 hour, 4, 11 and 23 hours, on Day 2 at 11 and 23 hours and on Day 5 at 0 hour, 1 hour, 4, 11, 23, 35 and 47 hours

• Pupillometry parameter: Amplitude of constriction

  Day 1 at 0 hour, 4, 11 and 23 hours, on Day 2 at 11 and 23 hours and on Day 5 at 0 hour, 1 hour, 4, 11, 23, 35 and 47 hours

• Pupillometry parameter: Onset latency of miosis

  Day 1 at 0 hour, 4, 11 and 23 hours, on Day 2 at 11 and 23 hours and on Day 5 at 0 hour, 1 hour, 4, 11, 23, 35 and 47 hours

• Pupillometry parameter: Constriction time

  Day 1 at 0 hour, 4, 11 and 23 hours, on Day 2 at 11 and 23 hours and on Day 5 at 0 hour, 1 hour, 4, 11, 23, 35 and 47 hours

• Minimum plasma concentration during dosing interval τ at steady-state (Css,min)

  predose on Day 1, during 4 consecutive days of multiple dosing and up to 72 hours after the last dosing on Day 5

Study Arms (4)

Group 1 (100 mg GRT0151Y)

EXPERIMENTAL

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.

Drug: 100 mg GRT0151Y; Drug: Matching placebo

Group 2 (125 mg GRT0151Y)

EXPERIMENTAL

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

Drug: 125 mg GRT0151Y; Drug: Matching placebo

Group 3 (150 mg GRT0151Y)

EXPERIMENTAL

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

Drug: 150 mg GRT0151Y; Drug: Matching placebo

Group 4 (225 mg GRT0151Y)

EXPERIMENTAL

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

Drug: 225 mg GRT0151Y; Drug: Matching placebo

Interventions

100 mg GRT0151Y DRUG

100 mg capsule (1 x 100 mg capsule)

Group 1 (100 mg GRT0151Y)

125 mg GRT0151Y DRUG

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

Group 2 (125 mg GRT0151Y)

150 mg GRT0151Y DRUG

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

Group 3 (150 mg GRT0151Y)

225 mg GRT0151Y 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)

Group 4 (225 mg GRT0151Y)

Matching placebo DRUG

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

Group 1 (100 mg GRT0151Y); Group 2 (125 mg GRT0151Y); Group 3 (150 mg GRT0151Y); Group 4 (225 mg GRT0151Y)

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (1)

ASTER

Paris, 75015, France

Location

MeSH Terms

Conditions

Acute Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Twelve volunteers (6 males and 6 females) per dose group will be randomly assigned to two treatment sequences (placebo-verum and verum-placebo, within dose-group randomized) in a ratio of 1:1. There will be a washout period of 7 to 11 days between the treatment sequences.

Study Record Dates

• First Submitted: November 30, 2018
• First Posted: December 3, 2018
• Study Start: December 30, 2004
• Primary Completion: July 26, 2005
• Study Completion: July 26, 2005
• Last Updated: December 3, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)