Thorough QT/QTc (Corrected QT Interval) Study to Evaluate the Effect of Custirsen on Cardiac Repolarization

NCT01874561 | Completed Phase 1

• 1 other identifier: TV1011-TQT-108
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 3-arm, parallel-group, active- and placebo-controlled, double-blind, randomized study, to compare treatment with intravenous custirsen at 640 mg (highest intended therapeutic dose) with placebo. The purpose of this study is to assess the effect of custirsen treatment on cardiac conduction and repolarization (electrical activity of the heart) in healthy subjects. The positive control employed to demonstrate assay sensitivity consists of a group receiving a single oral dose of 400 mg moxifloxacin on day 7. The moxifloxacin arm is un-blinded but the ECG readings are blinded.

Conditions

Cardiac Conduction and Repolarization

Keywords

Custirsen sodium; TV1011; OGX-011; Thorough QT study; cancer

Outcome Measures

Primary Outcomes (1)

• Individually-corrected QT interval (QTcI)

  The primary ECG variable and endpoint for this study is the time-matched change from baseline in QTcI method on day 7 at each time point. Holter ECGs will be performed at baseline (day -1) and prior to the start of infusion on day 7 and 1, 2 (end of infusion), 2.5, 3, 4, 5, 6, 8, 12, 16, 20, and 23.5 hours after the start of infusion.

  Up to 23.5 hours after the start of study drug infusion on Day 7

Secondary Outcomes (16)

• Fridericia-corrected QT interval (QTcF)

  Up to 23.5 hours after study drug infusion on Day 7

• Heart rate, PR interval, QRS interval and uncorrected QT interval

  Up to 23.5 hours after study drug infusion on Day 7

• ECG morphological patterns

  Up to 23.5 hours after study drug infusion on Day 7

• QTc (QTcI and QTcF) Intervals

  Up to 23.5 hours after study drug infusion on Day 7

• Assay sensitivity

  Up to 23.5 hours after study drug infusion on Day 7

Study Arms (3)

Group 1

EXPERIMENTAL

Group 1: investigational product (custirsen) will receive: * 320 mg of custirsen + 5 mg of dexamethasone on day 1 * 480 mg of custirsen + 5 mg of dexamethasone on day 3 * 640 mg of custirsen + 3 mg of dexamethasone on day 5 * 640 mg of custirsen on day 7 under fasting conditions

Drug: Custirsen

Group 2

PLACEBO COMPARATOR

Group 2: placebo (normal saline) will receive: * placebo + 5 mg of dexamethasone on day 1 * placebo + 5 mg of dexamethasone on day 3 * placebo + 3 mg of dexamethasone on day 5 * placebo on day 7 under fasting conditions

Drug: Placebo

Group 3

ACTIVE COMPARATOR

Group 3: positive control (moxifloxacin) will receive: * placebo + 5 mg of dexamethasone on day 1 * placebo + 5 mg of dexamethasone on day 3 * placebo + 3 mg of dexamethasone on day 5 * 400 mg of moxifloxacin + placebo (immediately after moxifloxacin administration) on day 7 under fasting conditions

Drug: Moxifloxacin

Interventions

Custirsen DRUG

Custirsen will be administered iv using an infusion pump over a 2-hour period.

Also known as: custirsen sodium

Group 1

Placebo DRUG

Placebo (commercially available normal saline) will be administered iv using an infusion pump over a 2-hour period.

Also known as: Normal saline

Group 2

Moxifloxacin DRUG

Moxifloxacin (400 mg) will be administered orally with 240 mL of room temperature still water.

Group 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject is a man aged 18 through 45 years of age with a body mass index (BMI) of 18 through 30 kg/m2 at screening.
• The subject is in good health as determined by medical history, ECG, vital signs measurements, physical examination, and clinical laboratory tests.
• The subject must be able to understand and comply with the requirements of the study (eg, all medication, dietary, exercise, tobacco, and alcohol restrictions).
• The subject must provide written informed consent to participate in the study after reading the information and consent form, and after having an opportunity to discuss the study with the investigator or delegate.

You may not qualify if:

• The subject has an ECG abnormality that may interfere with the accurate assessment of the QT interval, including intraventricular conduction delays (QRS \>120 msec or PR \>200 as measured at the screening and check-in visits) and complete or incomplete bundle branch blocks.
• The subject has a resting QTcF interval of ≤360 msec and/or ≥450 msec measured at screening or day -2.
• The subject has a known clinically significant (in the opinion of the investigator) cardiovascular disorder, including coronary artery disease, valvular heart disease, cardiomyopathies, or an ECG abnormality suggestive of prior myocardial infarction, angina pectoris, chamber enlargement, or hypertrophy. Notwithstanding, subjects with known significant disorders will be excluded.
• The subject has a known clinically significant arrhythmia or rhythm disturbance observed on the screening and/or day -2 12-lead ECG.
• The subject has a supine pulse rate outside of the range of 40 to 100 bpm (following at least a 10-minute rest) measured at screening or day -2.
• The subject has a supine blood pressure outside of the range of 90 to 139 mm Hg systolic or 50 to 89 mm Hg diastolic (following at least a 10-minute rest) measured at screening and on day -2. Note: The blood pressure measurement may be repeated up to 3 times to meet eligibility requirements. In this case, the average of these 3 measurements must meet eligibility criteria.
• The subject reports a history of, or risk factors for, Torsades de Pointes (eg, congestive heart failure, serum electrolyte abnormalities) including a family history of arrhythmia, sudden unexplained death at a young age (before 40 years) in a first-degree relative, or long QT syndrome, or a personal history of syncope.
• The subject has low serum potassium and/or magnesium and/or corrected calcium blood levels (less than 3.5 milliequivalent/liter (mEq/L), 1.8 mEq/L, and 8.9 mg/dL, respectively) at screening and/or day-2.
• The subject has any condition that may possibly interfere with drug absorption, distribution, metabolism, or excretion (eg, previous surgery on the gastrointestinal tract \[including removal of parts of stomach, bowel, liver, gall bladder, or pancreas\] or stomach banding).
• The subject has used one of the prohibited drugs, substances or foods as follows:
• any investigational product within 60 days (or 5 half-lives, whichever is longer) preceding the study
• any prescription or nonprescription medication (including herbal remedies, vitamins, or dietary supplements) or vaccine within 14 days of the first day of study drug administration (day 1) or within 5 half-lives before the first day of study drug administration, whichever is longer. Exceptions are locally acting medications (eg, topical creams), which are not allowed within 5 days of study drug administration, and the occasional use of acetaminophen (up to 3 g/day) and ibuprofen (up to 1200 mg/day).
• consumption of grapefruit, grapefruit juice, Seville oranges, pomelo-containing products, within the 14 days prior to day -1 and then throughout the entire study
• consumption of excessive amounts of alcoholic beverages, defined as more than 3 drinks per day (beer, wine, or distilled spirits), or unwillingness to comply with the restricted use of alcohol during the study (96 hours prior to admission and until 48 hours after the last study drug administration), history of alcoholism, or evidence of drug/chemical abuse
• positive urine drug (cocaine, amphetamines, barbiturates, opiates, phencyclidine, benzodiazepines, tetrahydrocannabinol), cotinine, or alcohol screen at the screening visit or admission

Sponsors & Collaborators

• Achieve Life Sciences: lead
• Teva Branded Pharmaceutical Products R&D, Inc.: collaborator

Study Sites (1)

Teva Investigational Site 10565

Lenexa, Kansas, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

OGX-011; Saline Solution; Moxifloxacin

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: May 1, 2013
• First Posted: June 11, 2013
• Study Start: May 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: January 1, 2014
• Last Updated: October 10, 2016

Record last verified: 2016-10

Locations

US (1)