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Randomized, single-dose, double-blind, placebo and active controlled, four-period crossover study to evaluate the effect of deferiprone on QTc prolongation after administration of a single therapeutic (33 mg/kg) and supratherapeutic(50 mg/kg) oral doses of deferiprone in healthy volunteers as compared to placebo treatment.
Post-marketing study to evaluate the effect of deferiprone and deferiprone 3-O-glucuronide on QTc prolongation in healthy volunteers after administration of a single therapeutic (33 mg/kg) and supratherapeutic (50 mg/kg) oral dose of deferiprone and moxifloxacin (Avelox®).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A - Maximum Therapeutic Dose | Experimental | Single dose of 33 mg/kg rounded to the nearest 250 mg of deferiprone tablets |
|
| Treatment Arm B - Supratherapeutic Dose | Experimental | Single dose of 50 mg/kg rounded to the nearest 250 mg of deferiprone tablets |
|
| Arm C - Placebo Control | Experimental | Single dose of matching deferiprone and moxifloxacin placebo tablets. |
|
| Arm D - Positive Control | Experimental | Single dose of one 400 mg moxifloxacin tablet. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Deferiprone | Drug | Ferriprox 500 mg tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 33 mg/kg Deferiprone | Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | 24-hour interval |
| Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 50 mg/kg Deferiprone | Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | 24-hour interval |
| Maximum Postdose QT/QTc Interval | The maximum post-dose QT/QTc interval for deferiprone and placebo. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | 24-hour interval |
| Maximum Change From Baseline (dQT/dQTc) | Maximum Change From Baseline (dQT/dQTc) for deferiprone and placebo. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | 24-hour interval |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | Number of participants with adverse events following therapeutic and supratherapeutic doses of deferiprone | From administration of the first dose until 7 days +/- 1 day following the final dose |
| Cmax of Deferiprone and Deferiprone 3-O Glucuronide |
Not provided
Main Inclusion Criteria:
Healthy adult males or females, 18 - 45 years of age (inclusive).
Body weight ≥ 50 kg.
Body mass index (BMI) ≥ 19 and ≤ 32 kg/m2.
Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination).
Absolute neutrophil count (ANC) of >1.5x109/L.
12-lead ECGs which have no clinically significant findings as judged by the Principal Investigator (PI) or the PI's designee at screening and check-in of each study period,including:
Subject must be capable of providing written informed consent, and must voluntarily consent to participate in the study.
Willing to answer inclusion and exclusion criteria questionnaire at check-in.
Main Exclusion Criteria:
History or presence of significant respiratory, cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,neurologic, or psychiatric disease.
Disorders or surgery of the gastrointestinal tract which may interfere with drug absorption or may otherwise influence the PK of the investigational medicinal products (e.g. cholecystectomy, resections of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, endocrine disease, severe infections,acute inflammations, etc.).
Presence of liver impairment: aspartate aminotransferase (AST), alanine aminotransferase (ALT) above the normal reference range.
Presence of significant kidney impairment: serum creatinine higher than the normal reference range.
Allergy to band aids, adhesive dressing or medical tape.
Clinically significant history or presence of ECG abnormalities such as second- or third-degree atrioventricular block; evidence, or family history, of prolonged QT syndrome.
Sustained sitting systolic blood pressure of <90 mmHg or >140 mmHg, or diastolic blood pressure of >95 mmHg at screening or check-in of Period 1.
History or presence of hypersensitivity or idiosyncratic reaction to deferiprone, moxifloxacin, iron chelators, or quinolone antibiotics.
History or presence of:
History or presence of alcoholism or drug abuse within the past 2 years.
Used tobacco/nicotine-containing product for at least 3 months prior to the first dose of study.
Used Depo-Provera® or levonorgestrel implant within 90 days prior to the first dose and throughout the study.
Participation in another clinical trial within 28 days prior to the first dose of the study.
Had a clinically significant illness during the 4 weeks prior to check-in on Day -1 of Period 1.
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| Name | Affiliation | Role |
|---|---|---|
| Fernando Tricta, MD | ApoPharma | Study Chair |
| Caroline Fradette, PhD | ApoPharma | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion | Tempe | Arizona | 85283 | United States |
Not provided
First subject enrolled: 17 November 2012 Last subject completed: 19 December 2012
The study was carried out at Celerion, a research facility used for conducting clinical trials.
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| ID | Title | Description |
|---|---|---|
| FG000 | ABCD | All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment A = single oral dose of 33 mg/kg deferiprone Treatment B = single oral dose of 50 mg/kg deferiprone Treatment C = single oral dose of placebo Treatment D = single oral dose of moxifloxacin |
| FG001 | BDAC | All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment B = single oral dose of 50 mg/kg deferiprone Treatment D = single oral dose of moxifloxacin Treatment A = single oral dose of 33 mg/kg deferiprone Treatment C = single oral dose of placebo |
| FG002 | CADB | All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment C = single oral dose of placebo Treatment A = single oral dose of 33 mg/kg deferiprone Treatment D = single oral dose of moxifloxacin Treatment B = single oral dose of 50 mg/kg deferiprone |
| FG003 | DCBA | All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order: Treatment D = single oral dose of moxifloxacin Treatment C = single oral dose of placebo Treatment B = single oral dose of 50 mg/kg deferiprone Treatment A = single oral dose of 33 mg/kg deferiprone |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Fifty subjects were enrolled in order to have at least 33 subjects complete the study. The sample size calculations were based on the ICH E14 Guidance which defines a negative TQT study as one "in which the upper bound of the 95% one-sided CI for the largest time-matched mean effect of the drug on the QTc interval excludes 10 msec."
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| ID | Title | Description |
|---|---|---|
| BG000 | All Subjects | Subjects in this cross-over study all received one dose of each the following: A) a maximum therapeutic dose of 33 mg deferiprone, B) a supratherapeutic dose of 50 mg/kg deferiprone, C) placebo, and D) moxifloxacin (active control). They were randomized to receive these products in different orders: ABCD, BDAC, CADB, or DCBA. Treatments were separated by a 7-day washout period. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 33 mg/kg Deferiprone | Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | Cardiodynamic Analysis Set : all randomized subjects who received at least 1 dose of study medication and who had valid Day 1 QT/QTc interval measurements (predose and at least one postdose measurement). | Posted | Least Squares Mean | Standard Deviation | milliseconds | 24-hour interval |
|
Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Arm A - Maximum Therapeutic Dose | Single dose of 33 mg/kg rounded to the nearest 250 mg of deferiprone tablets, deferiprone matching placebo tablets and one moxifloxacin matching placebo tablet. Deferiprone deferiprone matching placebo tablets moxifloxacin matching placebo tablet |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA Version 15.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Fernando Tricta, MD | ApoPharma Inc. | 416-401-7332 | ftricta@apopharma.com |
Not provided
| ID | Term |
|---|---|
| D000077543 | Deferiprone |
| D020084 | Long Interspersed Nucleotide Elements |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D011728 | Pyridones |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| deferiprone matching placebo tablets | Drug | deferiprone matching placebo tablets |
|
|
| moxifloxacin | Drug | Active control |
|
|
| placebo | Drug | moxifloxacin-matching placebo |
|
To evaluate the Cmax of deferiprone and deferiprone 3-O-glucuronide following administration of single doses of 33 and 50 mg/kg deferiprone in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. |
| 24-hour interval |
| Tmax of Deferiprone and Deferiprone 3-O-glucuronide | To evaluate the Tmax of deferiprone and deferiprone 3-O-glucuronide following administration of single doses of 33 and 50 mg/kg deferiprone in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | 24-hour interval |
| AUC0-infinity for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-infinity was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | 24-hour interval |
| T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | 24-hour interval |
| Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of Moxifloxacin | Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | 24-hour interval |
| Withdrawal by Subject |
|
| Personal reason |
|
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo Control | A single dose of deferiprone -matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water. |
|
|
|
| Secondary | Number of Participants With Adverse Events | Number of participants with adverse events following therapeutic and supratherapeutic doses of deferiprone | The Safety Analysis Set consisted of all subjects who received at least 1 dose of study medication and had at least 1 safety assessment. | Posted | Number | participants | From administration of the first dose until 7 days +/- 1 day following the final dose |
|
|
|
| Secondary | Cmax of Deferiprone and Deferiprone 3-O Glucuronide | To evaluate the Cmax of deferiprone and deferiprone 3-O-glucuronide following administration of single doses of 33 and 50 mg/kg deferiprone in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | The PK population consisted of all subjects who had taken study medication and had at least 1 PK sample collected. | Posted | Mean | Standard Deviation | μg/mL | 24-hour interval |
|
|
|
| Secondary | Tmax of Deferiprone and Deferiprone 3-O-glucuronide | To evaluate the Tmax of deferiprone and deferiprone 3-O-glucuronide following administration of single doses of 33 and 50 mg/kg deferiprone in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | The PK population consisted of all subjects who had taken study medication and had at least 1 PK sample collected. | Posted | Median | Full Range | hour | 24-hour interval |
|
|
|
| Secondary | AUC0-infinity for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-infinity was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | The PK population consisted of all subjects who had taken study medication and had at least 1 PK sample collected. | Posted | Mean | Standard Deviation | μg *hr/mL | 24-hour interval |
|
|
|
| Secondary | T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | The PK population consisted of all subjects who had taken study medication and had at least 1 PK sample collected. | Posted | Mean | Standard Deviation | hour | 24-hour interval |
|
|
|
| Primary | Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 50 mg/kg Deferiprone | Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | Cardiodynamic Analysis Set : all randomized subjects who received at least 1 dose of study medication and who had valid Day 1 QT/QTc interval measurements (predose and at least one postdose measurement). | Posted | Least Squares Mean | Standard Deviation | milliseconds | 24-hour interval |
|
|
|
|
| Primary | Maximum Postdose QT/QTc Interval | The maximum post-dose QT/QTc interval for deferiprone and placebo. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | The Cardiodynamic Analysis Set consisted of all randomized subjects who received at least 1 dose of study medication and who had valid Day 1 QT/QTc interval measurements (predose and at least one postdose measurement). | Posted | Number | percentage of participants | 24-hour interval |
|
|
|
| Primary | Maximum Change From Baseline (dQT/dQTc) | Maximum Change From Baseline (dQT/dQTc) for deferiprone and placebo. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | The Cardiodynamic Analysis Set consisted of all randomized subjects who received at least 1 dose of study medication and who had valid Day 1 QT/QTc interval measurements (predose and at least one postdose measurement). | Posted | Number | percentage of participants | 24-hour interval |
|
|
|
| Secondary | Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of Moxifloxacin | Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose. | Cardiodynamic Analysis Set : all randomized subjects who received at least 1 dose of study medication and who had valid Day 1 QT/QTc interval measurements (predose and at least one postdose measurement). | Posted | Least Squares Mean | Standard Deviation | milliseconds | 24-hour interval |
|
|
|
|
| 0 |
| 46 |
| 12 |
| 46 |
| EG001 | Treatment Arm B - Supratherapeutic Dose | Single dose of 50 mg/kg rounded to the nearest 250 mg of deferiprone tablets, and one moxifloxacin matching placebo tablet. Deferiprone moxifloxacin matching placebo tablet | 0 | 48 | 35 | 48 |
| EG002 | Treatment Arm C - Placebo Control | Single dose of deferiprone matching placebo tablets and one moxifloxacin matching placebo tablet. deferiprone matching placebo tablets moxifloxacin matching placebo tablet | 0 | 45 | 10 | 45 |
| EG003 | Treatment Arm D - Positive Control | Single dose of deferiprone matching placebo tablets and one 400 mg moxifloxacin tablet. Deferiprone moxifloxacin | 0 | 46 | 5 | 46 |
| Sinus arrest | Cardiac disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Irritability | General disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Sensation of foreign body | General disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA Version 15.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA Version 15.1 | Systematic Assessment |
|
| Procedural dizziness | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Systematic Assessment |
|
| Electrocardiogram QRS complex prolonged | Investigations | MedDRA Version 15.1 | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA Version 15.1 | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA Version 15.1 | Systematic Assessment |
|
| Red blood cells urine positive | Investigations | MedDRA Version 15.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Formication | Nervous system disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Abnormal dreams | Psychiatric disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Metrorrhagia | Reproductive system and breast disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Nasal ulcer | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Systematic Assessment |
|
| Pallor | Vascular disorders | MedDRA Version 15.1 | Systematic Assessment |
|
All unpublished information given to the CRO by ApoPharma shall not be published or disclosed to a third party without the prior written consent of ApoPharma.
The data generated by this study are considered confidential information and the property of ApoPharma. This confidential information may be published only in collaboration with participating personnel from ApoPharma or upon ApoPharma written consent to publish the article.
| D018626 |
| Retroelements |
| D020071 | Interspersed Repetitive Sequences |
| D012091 | Repetitive Sequences, Nucleic Acid |
| D001483 | Base Sequence |
| D015394 | Molecular Structure |
| D001669 | Biochemical Phenomena |
| D055598 | Chemical Phenomena |
| D040342 | Genetic Structures |
| D055614 | Genetic Phenomena |
| D040481 | Genome Components |
| D016678 | Genome |
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| QTcF > 450 to ≤ 480 msec |
|
| QTcF > 480 to ≤ 500 msec |
|
| QTcF > 500 msec |
|
| QTcF >30 but ≤ 60 msec |
|
| QTcF >60 msec |
|