Prolonged QTc IntervalPhase 1NCT03951402
Effect of a Multiple-dose Oral Administration of CG5503 PR on the Electrical Activity of the Heart in 48 Healthy Men and Women
A Phase 1 study testing 100 mg CG5503 (tapentadol hydrochloride) PR tablet and 400 mg Moxifloxacin tablet (overencapsulated) in people with Prolonged QTc Interval and Pharmacokinetic, run by Grünenthal GmbH at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Prolonged QTc Interval, Pharmacokinetic
- What is being tested?
- 100 mg CG5503 (tapentadol hydrochloride) PR tablet and 400 mg Moxifloxacin tablet (overencapsulated)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2003to Aug 2003
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female Caucasian participants aged 45-65 years;
- Body mass index (BMI) between 19 and 27 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). Electrocardiogram (ECG) parameters and vitals signs must be in the ranges given in exclusion criteria 3-8 and 11-14, respectively) Minor deviations of laboratory values from the normal range may be accepted (except potassium and magnesium), 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 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).
Who cannot join
- 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;
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- 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;
- Resting pulse rate below 45 beats/min or above 90 beats per minute;
- Systolic blood pressure above 160 mmHg or below 100 mmHg;
- Diastolic blood pressure above 95 mmHg or below 50 mmHg;
- History of drug allergy;
- Bronchial asthma;
- Participation in another clinical trial within the last three months before starting this study (exception: characterisation of metaboliser status);
- Blood donation (more than 100 milliliters) in the last three months before the start of the study;
- History or evidence of alcohol or drug abuse;
- Positive drug abuse screening test;
- Extremely unbalanced diet (in the opinion of the investigator);
- Excessive consumption of food or beverages containing caffeine (more than 1000 milliliters of coffee per day or other equivalent amounts of caffeine);
- Known or suspected of not being able to comply with the study protocol;
- Not able to communicate meaningfully with the investigator and staff;
- Neurotic personality, psychiatric illness, or suicide risk;
- History of seizures;
- Known hypersensitivity to opioids or quinolones;
- Pregnancy (for female participants);
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Investigation of the Effect on the QT/QTc Interval After Multiple Dose Oral Administration (100 and 200 mg Bid) of CG5503 PR in a Randomised, Double-blind, Double-dummy Placebo- and Moxifloxacin-controlled 4- Way Cross-over Phase I Study in 48 Healthy Male and Female Volunteers
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.
- Conditions
- Prolonged QTc Interval, Pharmacokinetic
- Being tested
- 100 mg CG5503 (tapentadol hydrochloride) PR tablet, Placebo matching CG5503 PR tablet, Placebo matching moxifloxacin capsule, 400 mg Moxifloxacin tablet (overencapsulated)
- Keywords
- QT/QTc Interval
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
100 mg CG5503 (tapentadol hydrochloride) PR tabletDrug
100 mg CG5503 (tapentadol hydrochloride) PR tablet.
Placebo matching CG5503 PR tabletDrug
Matching placebo tablet to CG5503 PR tablet.
Placebo matching moxifloxacin capsuleDrug
Matching placebo capsule to moxifloxacin capsule.
400 mg Moxifloxacin tablet (overencapsulated)Drug
Overencapsulated 400 mg Moxifloxacin tablet.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: 100 mg CG5503 (tapentadol hydrochloride) PR tablet; Drug: Placebo matching CG5503 PR tablet; Drug: 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. Receives: Drug: 100 mg CG5503 (tapentadol hydrochloride) PR tablet; Drug: 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. Receives: Drug: Placebo matching CG5503 PR tablet; Drug: 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. Receives: Drug: Placebo matching CG5503 PR tablet; Drug: Placebo matching moxifloxacin capsule; Drug: 400 mg Moxifloxacin tablet (overencapsulated) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
In addition to the corrected QT by regression as described for the primary endpoint, QTc was calculated by the following formulas: Fridericia, Framingham, and Bazett.
Measured: Baseline (Day 0) to Day 3
Incidence of treatment emergent adverse events
Number of adverse events and number of participants with adverse events.
Measured: 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
The clinical opiate withdrawal scale (COWS) assessment consisted of 11 questions which rated the severity of opiate withdrawal symptoms, including resting pulse rate, gastrointestinal upset, sweating, restlessness, pupil size, tremor, anxiety or irritability, bone or joint aches, gooseflesh skin, yawning, and runny nose or tearing. Each symptom was rated on a scale from 0 (not present) to 4 or 5 (most severe). The total score was calculated by summing the 11 individual scores. Scores from 0 to 4 are considered "no withdrawal", from 5 to 12 "mild withdrawal", from 13 to 24 "moderate withdrawal", 25 to 36 "moderately severe withdrawal" and above 36 "severe withdrawal".
Measured: Day 4 and Day 5
Pharmacokinetic parameter: Cmax(4-6h) of CG5503 base after the first dose
Maximum serum concentration in the observed time interval between 4 and 6 hours [Cmax(4-6h)]. Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration. Concentrations of CG5503 base in serum were determined by using validated High Performance Liquid Chromatography (HPLC) methods with fluorometric detection.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: tmax(4-6h) of CG5503 base after the first dose
Time to reach maximum serum concentration in the observed time interval between 4 and 6 hours [tmax(4-6h)]. Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: AUCss of CG5503 base after the last dose
Area under the concentration vs. time curve in dosing interval τ at steady state (AUCss). Blood samples for the determination of serum concentrations were taken at pre-dose and at up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: AUC of CG5503 base after the last dose
Area under the concentration vs. time curve (AUC) after the last dose. Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: AUCextr of CG5503 base after the last dose
Extrapolated part to infinity of AUC (AUCextr) after the last dose. Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: AUC%extr of CG5503 base after the last dose
Extrapolated part to infinity of AUC in percent (AUC%extr) after the last dose.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: Css,min of CG5503 base after the last dose
Minimum observed serum concentration during dosing interval τ at steady state (Css,min). Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: Css,max of CG5503 base after the last dose
Maximum observed serum concentration during dosing interval τ at steady state (Css,max). Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: Css,ave of CG5503 base after the last dose
Average serum concentration during dosing interval τ at steady state (Css,ave). Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: tss,max of CG5503 base after the last dose
Time to reach maximum serum concentration during dosing interval τ at steady state (tss,max). Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: λz of CG5503 base after the last dose
Apparent terminal elimination rate constant (λz) after the last dose. Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: t½,z of CG5503 base after the last dose
Apparent terminal half-life (t½,z) after the last dose. Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: CL/f of CG5503 base after the last dose
Apparent oral clearance at steady state (CL/f). Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: PTF (%) of CG5503 base after the last dose
Peak-trough fluctuation at steady state (PTF). Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Pharmacokinetic parameter: RA(Cmax) of CG5503 base after the last dose
Accumulation ratio (RA) calculated from Css,max at steady state and Cmax(4-6 hours) after single dosing. Blood samples for the determination of serum concentrations were taken at pre-dose and up to 12 hours on Day 1, prior to the morning and the evening dose on Day 2 and before and up to 48 hours after the last drug administration.
Measured: Day 1 to Day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2019
- Study startMar 2003
- Primary completionAug 2003
- Study completionAug 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prolonged QTc IntervalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grünenthal GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Grünenthal Study Director, Study director, Grünenthal GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03951402
- Sponsor's protocol ID
- HP5503/10
- Other IDs
- PK614
- Status last verified
- May 2019
- First submitted
- 14 May 2019
- Last updated
- 17 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Effect on the QT/QTc Interval After Multiple Dose Oral Administration (100 and 200 mg Bid) of CG5503 PR in a Randomised, Double-blind, Double-dummy Placebo- and Moxifloxacin-controlled 4- Way Cross-over Phase I Study in 48 Healthy Male and Female Volunteers
- ClinicalTrials.gov ID
- NCT03951402
- Acronym / sponsor ID
- HP5503/10
- Conditions
- Prolonged QTc Interval, Pharmacokinetic
- Keywords
- QT/QTc Interval
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Grünenthal GmbHIndustry (pharma, biotech, devices)
- Study start
- Mar 2003 (actual)
- Primary completion
- Aug 2003 (actual)
- Study completion
- Aug 2003 (actual)
- First posted
- 15 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| CG5503 PR 100 mg twice daily (tapentadol hydrochloride) | Experimental | Drug: 100 mg CG5503 (tapentadol hydrochloride) PR tablet, Drug: Placebo matching CG5503 PR tablet, Drug: Placebo matching moxifloxacin capsuleEach 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. |
| CG5503 PR 200 mg twice daily (tapentadol hydrochloride) | Experimental | Drug: 100 mg CG5503 (tapentadol hydrochloride) PR tablet, Drug: Placebo matching moxifloxacin capsuleEach 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. |
| Placebo | Placebo comparator | Drug: Placebo matching CG5503 PR tablet, Drug: Placebo matching moxifloxacin capsuleEach 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. |
| Moxifloxacin 800 mg single dose | Active comparator | Drug: Placebo matching CG5503 PR tablet, Drug: Placebo matching moxifloxacin capsule, Drug: 400 mg Moxifloxacin tablet (overencapsulated)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. |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female Caucasian participants aged 45-65 years;
- Body mass index (BMI) between 19 and 27 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). Electrocardiogram (ECG) parameters and vitals signs must be in the ranges given in exclusion criteria 3-8 and 11-14, respectively) Minor deviations of laboratory values from the normal range may be accepted (except potassium and magnesium), 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 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;
Key exclusion criteria (28 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 100 mg CG5503 (tapentadol hydrochloride) PR tablet100 mg CG5503 (tapentadol hydrochloride) PR tablet. | Drug | CG5503 PR 100 mg twice daily (tapentadol hydrochloride), CG5503 PR 200 mg twice daily (tapentadol hydrochloride) |
| Placebo matching CG5503 PR tabletMatching placebo tablet to CG5503 PR tablet. | Drug | CG5503 PR 100 mg twice daily (tapentadol hydrochloride), Moxifloxacin 800 mg single dose, Placebo |
| Placebo matching moxifloxacin capsuleMatching placebo capsule to moxifloxacin capsule. | Drug | CG5503 PR 100 mg twice daily (tapentadol hydrochloride), CG5503 PR 200 mg twice daily (tapentadol hydrochloride), Moxifloxacin 800 mg single dose, Placebo |
| 400 mg Moxifloxacin tablet (overencapsulated)Overencapsulated 400 mg Moxifloxacin tablet. | Drug | Moxifloxacin 800 mg single dose |
Primary outcome
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
Time frame: Baseline (Day 0) to Day 3
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.
18 secondary outcomes
The differences of the QTc at each time point on Day 3 to the time matched QTc on Day 0 of each period
Time frame: Baseline (Day 0) to Day 3
Incidence of treatment emergent adverse events
Time frame: 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
Time frame: Day 4 and Day 5
Pharmacokinetic parameter: Cmax(4-6h) of CG5503 base after the first dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: tmax(4-6h) of CG5503 base after the first dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: AUCss of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: AUC of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: AUCextr of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: AUC%extr of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: Css,min of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: Css,max of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: Css,ave of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: tss,max of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: λz of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: t½,z of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: CL/f of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: PTF (%) of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Pharmacokinetic parameter: RA(Cmax) of CG5503 base after the last dose
Time frame: Day 1 to Day 5
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Grünenthal Study Director study director
Grünenthal GmbH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 100 mg CG5503 (tapentadol hydrochloride) PR tablet and 400 mg Moxifloxacin tablet (overencapsulated) in people with Prolonged QTc Interval and Pharmacokinetic, run by Grünenthal GmbH at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Baseline (Day 0) to Day 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2019.