NCT03951402

Brief Summary

The effect of multiple oral administration of two doses of CG5503 PR (prolonged release) compared to placebo on the electrical activity of the heart were investigated. The rationale to perform this study was to exclude any effect of CG5503 on the heart rhythm. This study was a randomised, double-blind, double-dummy, placebo- and moxifloxacin-controlled, 4-way cross-over study. Participants were given a combination of either CG5503 PR and placebo (medication with inactive ingredients which looks like the study drug) or moxifloxacin and placebo. Moxifloxacin was used as a positive control. It has consistently shown that it has an effect on the heart rhythm. Within 14 days prior to the first dosing, participants had a physical examination, a 12-lead electrocardiogram (ECG) was recorded and haematological, serological, biochemical, and urine analyses took place. A blood sample for optional genotyping of genes responsible for long QT syndrome was taken. During each dosing session, the participants were confined in the evening before baseline assessments were performed and stayed in the clinic until 48 hours after the last dosing. Study medication was administered on Day 1 and 2 in the morning (0.5 hours after breakfast) and in the evening (1.5 hours after dinner), and on Day 3 in the morning (0.5 hours after breakfast). Dosing was separated by at least 7 days between the last dosing of each period and the first dosing of next period. Interim analysis of ECG-data were performed after completion of 24 participants (group 1) with possible subsequent adjustment of sample size for group 2.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Mar 2003

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2003

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2003

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2003

Completed
15.8 years until next milestone

First Submitted

Initial submission to the registry

May 14, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 15, 2019

Completed
Last Updated

May 17, 2019

Status Verified

May 1, 2019

Enrollment Period

5 months

First QC Date

May 14, 2019

Last Update Submit

May 15, 2019

Conditions

Prolonged QTc IntervalPharmacokinetic

Keywords

QT/QTc Interval

Outcome Measures

Primary Outcomes (1)

  • The mean of corrected QT interval (QTc) differences on Day 3 at 3 to 7 hours to matched time points on Day 0 of the respective treatment period

    On Day 0 drug-free baseline 12-lead ECGs were recorded (in supine position after at least 10 minutes of rest) at time points corresponding to those on Day 3. On Day 3, 12-lead ECGs were recorded prior to and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 24 hours after dosing. A regression analysis was applied for each participant to obtain an individual correction.

    Baseline (Day 0) to Day 3

Secondary Outcomes (18)

  • The differences of the QTc at each time point on Day 3 to the time matched QTc on Day 0 of each period

    Baseline (Day 0) to Day 3

  • Incidence of treatment emergent adverse events

    Day 1 to Day 5

  • Withdrawal symptoms: 5 categories of COWS scale, sum of scores (of 11 items) and changes to placebo in sum of scores

    Day 4 and Day 5

  • Pharmacokinetic parameter: Cmax(4-6h) of CG5503 base after the first dose

    Day 1 to Day 5

  • Pharmacokinetic parameter: tmax(4-6h) of CG5503 base after the first dose

    Day 1 to Day 5

  • +13 more secondary outcomes

Study Arms (4)

CG5503 PR 100 mg twice daily (tapentadol hydrochloride)

EXPERIMENTAL

Each participant received a morning and an evening dose of 100 mg CG5503 PR on days 1 and 2 and a morning dose on Day 3 (each dose: 1 tablet CG5503 PR and 1 placebo-tablet, matching CG5503 PR); additionally at each dosing each participant received 2 placebo-capsules, matching moxifloxacin 400 mg. The participants received 2 tablets and 2 capsules at each dosing with approximately 150 ml water.

Drug: 100 mg CG5503 (tapentadol hydrochloride) PR tabletDrug: Placebo matching CG5503 PR tabletDrug: Placebo matching moxifloxacin capsule

CG5503 PR 200 mg twice daily (tapentadol hydrochloride)

EXPERIMENTAL

Each participant received a morning and an evening dose of 200 mg CG5503 PR on days 1 and 2 and a morning dose on Day 3 (each dose: 2 tablets CG5503 PR); additionally at each dosing each participant received 2 placebo-capsules, matching moxifloxacin. The participants received 2 tablets and 2 capsules at each dosing with approximately 150 ml water.

Drug: 100 mg CG5503 (tapentadol hydrochloride) PR tabletDrug: Placebo matching moxifloxacin capsule

Placebo

PLACEBO COMPARATOR

Each participant received a morning and an evening dose of placebo to CG5503 PR on days 1 and 2 and a morning dose on Day 3 (each dose: 2 tablets placebo, matching CG5503 PR); additionally at each dosing each participant received 2 placebo-capsules, matching moxifloxacin. The participants received 2 tablets and 2 capsules at each dosing with approximately 150 ml water.

Drug: Placebo matching CG5503 PR tabletDrug: Placebo matching moxifloxacin capsule

Moxifloxacin 800 mg single dose

ACTIVE COMPARATOR

Each participant received a morning and an evening dose of placebo to CG5503 PR on days 1 and 2 and a morning dose on Day 3 (each dose: 2 tablets placebo, matching CG5503 PR); and 2 placebo-capsules, matching moxifloxacin on days 1 and 2; In the morning of Day 3, each participant received additionally 2 capsules each containing 1 tablet moxifloxacin. The participants received 2 tablets and 2 capsules at each dosing with approximately 150 ml water.

Drug: Placebo matching CG5503 PR tabletDrug: Placebo matching moxifloxacin capsuleDrug: 400 mg Moxifloxacin tablet (overencapsulated)

Interventions

100 mg CG5503 (tapentadol hydrochloride) PR tabletDRUG

100 mg CG5503 (tapentadol hydrochloride) PR tablet.

CG5503 PR 100 mg twice daily (tapentadol hydrochloride)CG5503 PR 200 mg twice daily (tapentadol hydrochloride)
Placebo matching CG5503 PR tabletDRUG

Matching placebo tablet to CG5503 PR tablet.

CG5503 PR 100 mg twice daily (tapentadol hydrochloride)Moxifloxacin 800 mg single dosePlacebo
Placebo matching moxifloxacin capsuleDRUG

Matching placebo capsule to moxifloxacin capsule.

CG5503 PR 100 mg twice daily (tapentadol hydrochloride)CG5503 PR 200 mg twice daily (tapentadol hydrochloride)Moxifloxacin 800 mg single dosePlacebo
400 mg Moxifloxacin tablet (overencapsulated)DRUG

Overencapsulated 400 mg Moxifloxacin tablet.

Moxifloxacin 800 mg single dose

Eligibility Criteria

Age45 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female Caucasian participants aged 45-65 years;
  • Body mass index (BMI) between 19 and 27 kilograms/square meter inclusive;

You may not qualify if:

  • Negative human immunodeficiency virus (HIV) 1/2 -antibodies, hepatitis B surface (HBs)-antigen, hepatitis B core (HBc)-antibodies and hepatitis C virus (HCV)-antibodies at the prestudy medical examination;
  • Negative blood beta-human chorionic gonadotropine (HCG)-test for women of child bearing potential;
  • Participants giving written consent to participate within this study;
  • Participants giving written consent for blood sampling to be genotyped for genes responsible for long QT syndrome (KCNQ1, human ether-a-go-go-related gene (HERG), SCN5A, KCNE1, KCNE2, KCNJ2).
  • Regular use of any medication within four weeks prior to commencement of the study (self-medication or prescription except for hormonal contraception and HRT);
  • Smoker more than 5 cigarettes per day;
  • No regular sinus rhythm;
  • ECG interval: QRS complex above 100 millisecond;
  • ECG interval: PQ above 200 milliseconds;
  • ECG interval: RR above 1333 milliseconds;
  • QT/QTc intervals above 450 milliseconds;
  • Known family history of sudden cardiac death and arrhythmias;
  • Diseases and functional disorders of the gastrointestinal tract, liver, cardiovascular system or kidneys;
  • Malignancy;
  • History of orthostatic hypotension;
  • +17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

DE001 - Contract research organisation

Neuss, 41460, Germany

Location

MeSH Terms

Interventions

TapentadolMoxifloxacin

Intervention Hierarchy (Ancestors)

PhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsFluoroquinolones4-QuinolonesQuinolonesQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Grünenthal Study Director

    Grünenthal GmbH

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Model Details: This study was a randomized, double-blind, double-dummy, placebo- and moxifloxacin-controlled, 4-way cross-over study. The randomization was in the ratio 1:1:1:1. In all treatments the amount of administered tablets and capsules were the same. At the lower dose step the amount of tablets/capsules was adjusted with matching placebos. All study procedures were the same, irrespective of whether active compound, positive control or placebo was administered.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 14, 2019

First Posted

May 15, 2019

Study Start

March 1, 2003

Primary Completion

August 1, 2003

Study Completion

August 1, 2003

Last Updated

May 17, 2019

Record last verified: 2019-05

Data Sharing

IPD Sharing
Will not share

Locations

DE(1)