Evaluation of the Effects of Multiple Doses of Cebranopad... | NCT03958123

NCT03958123

Status Module

Name	Class
Forest Laboratories	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment Group 1: Cebranopadol	Experimental	Supratherapeutic dose (1600 μg) of cebranopadol: Participants received placebo once a day for 2 days (Days -3 and -1); 200 μg of cebranopadol once a day for 3 days; 400 μg once a day for 3 days; 600 μg once a day for 3 days; 900 μg once a day for 3 days; 1300 μg once a day for 3 days; 1600 μg once a day for 14 days; and placebo once a day on the last dosing day. Participants received capsules under fasting conditions on Days -3, -1, 1, 29 and 30, and under fed conditions on all other dosing days. Participants received four encapsulated cebranopadol/ placebo tablets and 1 encapsulated moxifloxacin/ placebo tablet (5 capsules in total) on Day -3, Day -1, and from Day 1 to Day 30. Capsules were taken with 240 mL of water.	Drug: 100 μg cebranopadol Drug: 200 μg cebranopadol Drug: 400 μg cebranopadol Drug: Placebo to cebranopadol encapsulated tablets Drug: Placebo to moxifloxacin encapsulated tablets
Treatment Group 2: Cebranopadol	Experimental	Therapeutic dose (600 μg) of cebranopadol: Participants received placebo once a day for the first 11 days (Days -3, -1 and 1-9); 200 μg of cebranopadol once a day for 3 days; 400 μg once a day for 3 days; 600 μg once a day for 14 days; and placebo once a day on the last dosing day. Participants received capsules under fasting conditions on Days -3, -1, 1, 29 and 30, and under fed conditions on all other dosing days. Participants received 4 encapsulated cebranopadol/ placebo tablets and 1 encapsulated moxifloxacin/ placebo tablet (5 capsules in total) on Day -3, Day -1, and from Day 1 to Day 30. Capsules were taken with 240 mL of water.	Drug: 200 μg cebranopadol Drug: 400 μg cebranopadol Drug: Placebo to cebranopadol encapsulated tablets Drug: Placebo to moxifloxacin encapsulated tablets
Treatment Group 3A: Placebo and Moxifloxacin	Experimental

Name	Type	Description	Arm Group Labels	Other Names
100 μg cebranopadol	Drug	Encapsulated 100 μg cebranopadol tablet.	Treatment Group 1: Cebranopadol

Measure	Description	Time Frame
QTcNi change from time-matched baseline measurement on Day -1 to Day 29 - supported sitting position	Largest time-matched mean difference between cebranopadol and placebo in supported sitting QT interval corrected for heart rate using an individual correction (QTcNi) change from time-matched baseline measurement on Day -1.	Day -1 up to Day 29

Measure	Description	Time Frame
QTcNi change from time-matched baseline measurement on Day -1 to Day 29 - supine position	Largest time-matched mean difference between cebranopadol and placebo in supine QTcNi change from time-matched baseline measurement on Day -1.	Day -1 up to Day 29
QTcF change from time-matched baseline measurement on Day -1 to Day 29 - sitting position

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Sign the informed consent form (ICF) and have the mental capability to understand it.
Be a healthy male or female, aged 18 through 45 years, inclusive.
If female, have a negative result from a serum pregnancy test at screening and a negative result from a serum or urine pregnancy test on Day -4.
If male, agree to use an effective method of contraception (ie, condom plus diaphragm with spermicide or condom plus spermicide) and not have their partners become pregnant throughout the study, or have been sterilized for at least 1 year (with supporting documentation of the absence of sperm in the ejaculate postvasectomy).
If female of childbearing potential, agree to use an effective method of contraception (ie, condom plus diaphragm with spermicide, condom plus spermicide, or nonhormonal intrauterine device) and not become pregnant throughout the study. Females who are at least 2-years postmenopausal (with supporting documentation from an obstetrician/gynecologist) or who have had tubal ligation or hysterectomy (with supporting documentation from the physician who performed the surgery) will not be considered to be of childbearing potential.
Be nonsmoking (never smoked or have not smoked within the previous 2 years).
Have a body mass index (BMI) greater than or equal to 18 kilograms per square meter and less than or equal to 30 kilograms per square meter.
Have a sitting pulse rate greater than or equal to 50 beats per minute (bpm) and less than or equal to 100 bpm during the vital sign assessment at screening.

Exclusion Criteria:

Known hypersensitivity to cebranopadol, other opioids, or moxifloxacin or other fluoroquinolone antibiotics.
Clinically significant disease state, in the opinion of the examining physician, in any body system.
Sitting systolic blood pressure (BP) greater than or equal to 140 millimeters mercury (mm Hg) or less than or equal to 90 mm Hg or sitting diastolic BP greater than or equal to 90 mm Hg or less than or equal to 50 mm Hg at screening.
Abnormal electrocardiogram (ECG) results thought to be potentially clinically significant (PCS), or QT prolongation (QTcF greater than or equal to 450 milliseconds (msec) or uncorrected QT greater than or equal to 500 msec) according to the Investigator.
History of cardiovascular disease including but not limited to long QT syndrome (or family history of long QT syndrome), cardiac arrhythmia, orthostatic hypotension, and coronary artery or valvular disease.
Positive test results for anti-human immunodeficiency virus type 1, hepatitis B surface antigen, hepatitis B core antibodies, or anti-hepatitis C virus at screening.
Abnormal and clinically significant results on medical history, physical examination, serum chemistry, hematology, or urinalysis.
History of alcohol or other substance abuse within the previous 5 years.
Positive urine drug screen test results for benzoylecgonine (cocaine), methadone, barbiturates, amphetamines, benzodiazepines, alcohol, cannabinoids, opiates, phencyclidine, or cotinine at screening or Day -4.
Have taken opioids within the past 1 month.
Participation in any other clinical investigation using an experimental drug requiring repeated blood or plasma draws within 60 days of investigational product administration.
Participation in a blood or plasma donation program within 60 or 30 days, respectively, of investigational product administration.
Consumption of caffeine products within 48 hours or any grapefruit-containing products or Seville oranges within 14 days or consumption of alcohol or poppy seeds within 72 hours before administration of investigational product.
Consumption of beverages or food containing quinine (bitter lemon, tonic water) within 14 days before administration of investigational product until discharge from the study center.
Have any clinical condition that might affect the absorption, distribution, biotransformation, or excretion of cebranopadol or moxifloxacin.
Employee, or immediate relative of an employee, of Forest Laboratories, Inc. or Grünenthal GmbH, any of its affiliates or partners, or the study center.
Taken any concomitant medications (including over-the-counter medications) within 14 days or hormonal drug products within 30 days before administration of investigational product.
Previously taken cebranopadol or previously participated in an investigational study of cebranopadol.
Breastfeeding.
Responses to the Columbia-Suicide Severity Rating Scale (C-SSRS) that indicate any current suicidal ideation or a history of active suicidal ideation or suicide attempts.
Suicidal risk based on the opinion of the principal investigator (or appropriately trained designee).

ID	Term
C000589289	6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenylspiro(cyclohexane-1,1'(3'H)-pyrano(3,4-b)indol)-4-amine
D000077266	Moxifloxacin

ID	Term
D024841	Fluoroquinolones
D042462	4-Quinolones
D015363	Quinolones
D011804	Quinolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds