Evaluation of the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration of ICL670 Relative to Deferoxamine(DFO).
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01090323
Collaborator
(none)
185
39
1
4.7
Study Details
Study Description
Brief Summary
The safety, tolerability, effects on liver iron concentration and pharmacokinetics of ICL670 is studied in sickle cell disease patients with transfusional hemosiderosis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
The treatment period started once the patient completed the core study and signed informed consent. It is continued for up to 4 years. Safety parameters were assessed every 4 weeks. Eye and Ear examinations were performed on a yearly basis. To further investigate the extent of iron overload, serum ferritin, iron, and transferrin were monitored every four weeks. The Program Safety Board monitored the safety of ICL670 during the study to evaluate and categorize any serious case reported in association with ICL670.
Study Design
Study Type:
Interventional
Actual Enrollment
:
185 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A One Year Open Label, Non-comparative Extension to a Randomized, Multicenter, Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration (LIC) of Repeated Doses of 5-30mg/kg/Day ICL670 Relative to Deferoxamine (DFO) in Sickle Cell Disease (SCD) Patients With Transfusional Hemosideresis (THS) [Amendment 3: Extension Prolonged to 4-years]
Study Start Date
:
Jul 1, 2004
Actual Primary Completion Date
:
Jul 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ICL670
|
Drug: ICL670
Daily doses of ICL670 were taken orally 30 minutes before breakfast. The doses range from 5-40 mg/kg and were determined based on the patient's trend in serum ferritin over time during the core study (0109) and on the frequency of blood transfusions the patient received. The treatment duration was up to 4 years.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events After Start of ICL670 [0 - 60 months]
Safety as assessed by the number of participants with adverse event or death after the start of ICL670.
Secondary Outcome Measures
- Change in Serum Ferritin From Start of ICL670 to End of Study [0 - 60 months]
The main efficacy variable was change in serum ferritin in response to therapy with ICL670. Due to variability of serum ferritin, end of study was considered as the mean of at most the last 3 available observations after the start of ICL670.
Eligibility Criteria
Criteria
Ages Eligible for Study:
2 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Patients were included who met the following criteria:
-
Completion of the core [Study 0109]
-
Serum ferritin greater than or equal to 500 µg/L
-
Ability to comply with all study-related procedures, medications, and evaluations
-
Sexually active post-menarche female patients must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months.
-
Written informed consent and assent by the patient and or their parents or legal guardian.
Additional inclusion criteria for pediatric patients The definition of the term 'pediatric' for enrollment and study conduct was in accordance with local law. Parents or the legal guardians were fully informed by the investigator as to the requirements of the study. The pediatric patients themselves were informed according to their capabilities in a language and terms that they were able to understand. Written informed consent was obtained from their legal guardian on the patient's behalf in accordance with national legislation. If capable, all patients had to also personally sign their written informed consent.
Exclusion Criteria:
Patients who met the following criteria were to be excluded:
-
History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
-
Serum creatinine above the age-appropriate upper limit of normal within one week prior to entry
-
Patients with ALT ≥ 500 U/L within one week prior to entry
-
Evidence of chelation-related cataracts or hearing loss within 4 weeks prior to baseline
-
Pregnancy (as indicated by serum β-HCG pregnancy test for all female patients with the potential to become pregnant) and patients who are breastfeeding
-
Patients treated with systemic investigational drug within 4 weeks prior to or with topical investigational drug within 7 days prior to the baseline visit
Other protocol-defined inclusion/exclusion criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of South Alabama College of Medicine | Mobile | Alabama | United States | 36604 |
| 2 | Loma Linda University Medical Center | Loma Linda | California | United States | 92354 |
| 3 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
| 4 | Children's Hospital & Research Center at Oakland | Oakland | California | United States | 90609 |
| 5 | University of Colorado Health Science Center | Denver | Colorado | United States | 80262 |
| 6 | Howard University Hospital | Washington | District of Columbia | United States | 20059 |
| 7 | St Joseph Children's Hospital of Tampa | Tampa | Florida | United States | 33607 |
| 8 | Grady Hospital, Georgia Comprehensive Sickle Cell Center | Atlanta | Georgia | United States | 30303 |
| 9 | Medical College of Georgia | Augusta | Georgia | United States | 30912 |
| 10 | University of Illinois at Chicago | Chicago | Illinois | United States | 60612 |
| 11 | Children's Memorial Hospital | Chicago | Illinois | United States | 60614 |
| 12 | Tulane University Medical Center | New Orleans | Louisiana | United States | 70112 |
| 13 | LSUHSC Dept of Pediatrics | Shreveport | Louisiana | United States | 71130 |
| 14 | Children's Hospital Boston | Boston | Massachusetts | United States | 02118 |
| 15 | Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 16 | Montefiore Medical Center | Bronx | New York | United States | 10467 |
| 17 | New York Methodist Hospital | Brooklyn | New York | United States | 11215 |
| 18 | New York Presbyterian Hospital | New York | New York | United States | 10021 |
| 19 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
| 20 | Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
| 21 | University of Cincinnati | Cincinnati | Ohio | United States | 45267 |
| 22 | Milton S. Hershey Medical Center | Hershey | Pennsylvania | United States | 17033 |
| 23 | Yasin | Philadelphia | Pennsylvania | United States | 19104 |
| 24 | Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15213 |
| 25 | Palmetto Health Richland | Columbia | South Carolina | United States | 29203 |
| 26 | Santee Hematology/Oncology | Sumter | South Carolina | United States | 29150 |
| 27 | St. Jude's Children Research Hospital | Memphis | Tennessee | United States | 38105 |
| 28 | Texas Children's Hospital | Houston | Texas | United States | 77030 |
| 29 | The Methodist Hospital | Houston | Texas | United States | 77030 |
| 30 | Scott & White Memorial Hospital | Temple | Texas | United States | 76508 |
| 31 | Children's Hospital of the King's Daughters | Norfolk | Virginia | United States | 23507 |
| 32 | Novartis Investigative Site | Toronto | Canada | ||
| 33 | Novartis Investigative Site | Creteil | France | ||
| 34 | Novartis Investigative Site | Paris | France | ||
| 35 | Novartis Investigative Site | Catania | Italy | ||
| 36 | Novartis Investigative Site | Genova | Italy | ||
| 37 | Novartis Investigative Site | Milano | Italy | ||
| 38 | Novartis Investigative Site | Roma | Italy | ||
| 39 | Novartis Investigative Site | London | United Kingdom |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT01090323
Other Study ID Numbers:
- CICL670A0109E1
- EudraCT no. 2004-000597-31
- NCT00171197
First Posted:
Mar 19, 2010
Last Update Posted:
Jun 6, 2011
Last Verified:
May 1, 2011
Keywords provided by ,
,
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | ICL670 | Crossover |
|---|---|---|
| Arm/Group Description | Participants treated with ICL670 during the Core Study 0109(NCT00067080) and during the extension phase. ICL670 was administered orally once a day based on the participant's body weight. | Participants treated with Deferoxamine (DFO) during the Core Study 0109 (NCT00067080) and treated with ICL670 during the extension phase. ICL670 was administered orally once a day based on the participant's body weight. |
| Period Title: Overall Study | ||
| STARTED | 132 | 53 |
| COMPLETED | 43 | 19 |
| NOT COMPLETED | 89 | 34 |
Baseline Characteristics
| Arm/Group Title | ICL670 | Crossover | Total |
|---|---|---|---|
| Arm/Group Description | Participants treated with ICL670 during the Core Study 0109(NCT00067080) and during the extension phase. ICL670 was administered orally once a day based on the participant's body weight. | Participants treated with Deferoxamine (DFO) during the Core Study 0109 (NCT00067080) and treated with ICL670 during the extension phase. ICL670 was administered orally once a day based on the participant's body weight. | Total of all reporting groups |
| Overall Participants | 132 | 53 | 185 |
| Age, Customized (participants) [Number] | |||
| <12 years |
33
25%
|
14
26.4%
|
47
25.4%
|
| 12 - <16 years |
32
24.2%
|
11
20.8%
|
43
23.2%
|
| 16 - <65 years |
67
50.8%
|
28
52.8%
|
95
51.4%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
80
60.6%
|
31
58.5%
|
111
60%
|
| Male |
52
39.4%
|
22
41.5%
|
74
40%
|
| Region of Enrollment (participants) [Number] | |||
| France |
10
7.6%
|
2
3.8%
|
12
6.5%
|
| United States |
110
83.3%
|
46
86.8%
|
156
84.3%
|
| Canada |
0
0%
|
1
1.9%
|
1
0.5%
|
| United Kingdom |
5
3.8%
|
1
1.9%
|
6
3.2%
|
| Italy |
7
5.3%
|
3
5.7%
|
10
5.4%
|
Outcome Measures
| Title | Number of Participants With Adverse Events After Start of ICL670 |
|---|---|
| Description | Safety as assessed by the number of participants with adverse event or death after the start of ICL670. |
| Time Frame | 0 - 60 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The primary analysis was on Safety Analysis Set which comprised all participants who received at least one dose of ICL670 during the core/extension phase of the study. All participants previously treated with ICL670/DFO for 52weeks in the core study. |
| Arm/Group Title | ICL670 | Crossover |
|---|---|---|
| Arm/Group Description | Participants treated with ICL670 during the Core Study 0109(NCT00067080) and during the extension phase. ICL670 was administered orally once a day based on the participant's body weight. | Participants treated with Deferoxamine (DFO) during the Core Study 0109 (NCT00067080) and treated with ICL670 during the extension phase. ICL670 was administered orally once a day based on the participant's body weight. |
| Measure Participants | 132 | 53 |
| Adverse Events |
131
(10.66)
99.2%
|
49
(11.32)
92.5%
|
| Deaths |
1
0.8%
|
2
3.8%
|
| Title | Change in Serum Ferritin From Start of ICL670 to End of Study |
|---|---|
| Description | The main efficacy variable was change in serum ferritin in response to therapy with ICL670. Due to variability of serum ferritin, end of study was considered as the mean of at most the last 3 available observations after the start of ICL670. |
| Time Frame | 0 - 60 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The primary analysis was on Full Analysis Set which comprised all participants who received at least one dose of ICL670 during the core or the extension phase of the study. All participants previously treated with ICL670 or DFO for 52 weeks in the core study were eligible for enrollment. |
| Arm/Group Title | ICL670 | Crossover |
|---|---|---|
| Arm/Group Description | Participants treated with ICL670 during the Core Study 0109(NCT00067080) and during the extension phase. ICL670 was administered orally once a day based on the participant's body weight. | Participants treated with Deferoxamine (DFO) during the Core Study 0109 (NCT00067080) and treated with ICL670 during the extension phase. ICL670 was administered orally once a day based on the participant's body weight. |
| Measure Participants | 132 | 53 |
| Median (Full Range) [µg/L] |
-245.5
|
-134.3
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | ICL670 | Crossover | ||
| Arm/Group Description | Participants treated with ICL670 during the Core Study 0109(NCT00067080) and during the extension phase. ICL670 was administered orally once a day based on the participant's body weight. | Participants treated with Deferoxamine (DFO) during the Core Study 0109 (NCT00067080) and treated with ICL670 during the extension phase. ICL670 was administered orally once a day based on the participant's body weight. | ||
All Cause Mortality |
||||
| ICL670 | Crossover | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| ICL670 | Crossover | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 97/132 (73.5%) | 34/53 (64.2%) | ||
| Blood and lymphatic system disorders | ||||
| Acute chest syndrome | 5/132 (3.8%) | 3/53 (5.7%) | ||
| Anaemia | 1/132 (0.8%) | 2/53 (3.8%) | ||
| Anaemia haemolytic autoimmune | 1/132 (0.8%) | 0/53 (0%) | ||
| Coagulopathy | 1/132 (0.8%) | 0/53 (0%) | ||
| Haemolysis | 2/132 (1.5%) | 0/53 (0%) | ||
| Haemolytic anaemia | 1/132 (0.8%) | 0/53 (0%) | ||
| Hypersplenism | 1/132 (0.8%) | 0/53 (0%) | ||
| Leukocytosis | 1/132 (0.8%) | 0/53 (0%) | ||
| Lymphadenopathy | 1/132 (0.8%) | 0/53 (0%) | ||
| Spleen disorder | 1/132 (0.8%) | 0/53 (0%) | ||
| Splenomegaly | 1/132 (0.8%) | 0/53 (0%) | ||
| Thrombocytopenia | 1/132 (0.8%) | 0/53 (0%) | ||
| Cardiac disorders | ||||
| Arrhythmia | 1/132 (0.8%) | 0/53 (0%) | ||
| Cardiac failure congestive | 2/132 (1.5%) | 0/53 (0%) | ||
| Congenital, familial and genetic disorders | ||||
| Sickle cell anaemia | 0/132 (0%) | 1/53 (1.9%) | ||
| Sickle cell anaemia with crisis | 48/132 (36.4%) | 19/53 (35.8%) | ||
| Ear and labyrinth disorders | ||||
| Otorrhoea | 1/132 (0.8%) | 0/53 (0%) | ||
| Tinnitus | 0/132 (0%) | 1/53 (1.9%) | ||
| Eye disorders | ||||
| Vitreous haemorrhage | 0/132 (0%) | 1/53 (1.9%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 14/132 (10.6%) | 4/53 (7.5%) | ||
| Abdominal pain upper | 3/132 (2.3%) | 1/53 (1.9%) | ||
| Ascites | 1/132 (0.8%) | 0/53 (0%) | ||
| Constipation | 2/132 (1.5%) | 1/53 (1.9%) | ||
| Dental caries | 1/132 (0.8%) | 0/53 (0%) | ||
| Diarrhoea | 2/132 (1.5%) | 1/53 (1.9%) | ||
| Food poisoning | 0/132 (0%) | 1/53 (1.9%) | ||
| Gastrointestinal haemorrhage | 2/132 (1.5%) | 0/53 (0%) | ||
| Gastrointestinal inflammation | 1/132 (0.8%) | 0/53 (0%) | ||
| Nausea | 3/132 (2.3%) | 0/53 (0%) | ||
| Pancreatitis | 1/132 (0.8%) | 0/53 (0%) | ||
| Pancreatitis acute | 1/132 (0.8%) | 0/53 (0%) | ||
| Retroperitoneal haemorrhage | 1/132 (0.8%) | 0/53 (0%) | ||
| Tooth disorder | 1/132 (0.8%) | 0/53 (0%) | ||
| Varices oesophageal | 0/132 (0%) | 1/53 (1.9%) | ||
| Vomiting | 7/132 (5.3%) | 5/53 (9.4%) | ||
| General disorders | ||||
| Asthenia | 0/132 (0%) | 1/53 (1.9%) | ||
| Catheter related complication | 0/132 (0%) | 2/53 (3.8%) | ||
| Catheter site haemorrhage | 0/132 (0%) | 1/53 (1.9%) | ||
| Catheter site pain | 1/132 (0.8%) | 1/53 (1.9%) | ||
| Catheter thrombosis | 0/132 (0%) | 1/53 (1.9%) | ||
| Chest discomfort | 1/132 (0.8%) | 0/53 (0%) | ||
| Chest pain | 8/132 (6.1%) | 4/53 (7.5%) | ||
| Chills | 1/132 (0.8%) | 1/53 (1.9%) | ||
| Facial pain | 1/132 (0.8%) | 0/53 (0%) | ||
| Granuloma | 1/132 (0.8%) | 0/53 (0%) | ||
| Local swelling | 0/132 (0%) | 1/53 (1.9%) | ||
| Necrosis | 1/132 (0.8%) | 0/53 (0%) | ||
| Non-cardiac chest pain | 1/132 (0.8%) | 0/53 (0%) | ||
| Oedema peripheral | 1/132 (0.8%) | 0/53 (0%) | ||
| Pain | 6/132 (4.5%) | 1/53 (1.9%) | ||
| Pyrexia | 25/132 (18.9%) | 9/53 (17%) | ||
| Hepatobiliary disorders | ||||
| Bile duct stone | 1/132 (0.8%) | 0/53 (0%) | ||
| Biliary colic | 1/132 (0.8%) | 0/53 (0%) | ||
| Cholecystitis | 1/132 (0.8%) | 1/53 (1.9%) | ||
| Cholelithiasis | 7/132 (5.3%) | 2/53 (3.8%) | ||
| Hepatic cirrhosis | 1/132 (0.8%) | 0/53 (0%) | ||
| Hepatic failure | 1/132 (0.8%) | 0/53 (0%) | ||
| Hepatic sequestration | 1/132 (0.8%) | 0/53 (0%) | ||
| Hyperbilirubinaemia | 0/132 (0%) | 1/53 (1.9%) | ||
| Jaundice | 1/132 (0.8%) | 0/53 (0%) | ||
| Infections and infestations | ||||
| Abscess limb | 0/132 (0%) | 1/53 (1.9%) | ||
| Adenovirus infection | 1/132 (0.8%) | 0/53 (0%) | ||
| Appendicitis | 0/132 (0%) | 1/53 (1.9%) | ||
| Bacteraemia | 2/132 (1.5%) | 0/53 (0%) | ||
| Bronchitis | 3/132 (2.3%) | 2/53 (3.8%) | ||
| Catheter bacteraemia | 1/132 (0.8%) | 0/53 (0%) | ||
| Catheter related infection | 5/132 (3.8%) | 2/53 (3.8%) | ||
| Cellulitis | 3/132 (2.3%) | 1/53 (1.9%) | ||
| Central line infection | 1/132 (0.8%) | 1/53 (1.9%) | ||
| Endocarditis | 1/132 (0.8%) | 0/53 (0%) | ||
| Gastroenteritis | 2/132 (1.5%) | 3/53 (5.7%) | ||
| Gastroenteritis viral | 0/132 (0%) | 1/53 (1.9%) | ||
| Herpes zoster | 0/132 (0%) | 1/53 (1.9%) | ||
| Influenza | 1/132 (0.8%) | 1/53 (1.9%) | ||
| Lobar pneumonia | 1/132 (0.8%) | 0/53 (0%) | ||
| Lung infection | 1/132 (0.8%) | 0/53 (0%) | ||
| Mononucleosis syndrome | 1/132 (0.8%) | 0/53 (0%) | ||
| Osteomyelitis | 0/132 (0%) | 1/53 (1.9%) | ||
| Otitis media | 1/132 (0.8%) | 1/53 (1.9%) | ||
| Pharyngitis streptococcal | 0/132 (0%) | 1/53 (1.9%) | ||
| Pneumonia | 13/132 (9.8%) | 3/53 (5.7%) | ||
| Pneumonia bacterial | 1/132 (0.8%) | 0/53 (0%) | ||
| Pyelonephritis | 1/132 (0.8%) | 0/53 (0%) | ||
| Pyelonephritis acute | 1/132 (0.8%) | 0/53 (0%) | ||
| Respiratory syncytial virus infection | 1/132 (0.8%) | 0/53 (0%) | ||
| Sepsis | 3/132 (2.3%) | 1/53 (1.9%) | ||
| Sinusitis | 1/132 (0.8%) | 0/53 (0%) | ||
| Staphylococcal bacteraemia | 1/132 (0.8%) | 0/53 (0%) | ||
| Staphylococcal infection | 1/132 (0.8%) | 1/53 (1.9%) | ||
| Staphylococcal sepsis | 1/132 (0.8%) | 0/53 (0%) | ||
| Subcutaneous abscess | 0/132 (0%) | 1/53 (1.9%) | ||
| Tuberculosis | 1/132 (0.8%) | 0/53 (0%) | ||
| Upper respiratory tract infection | 3/132 (2.3%) | 3/53 (5.7%) | ||
| Urinary tract infection | 3/132 (2.3%) | 1/53 (1.9%) | ||
| Viral infection | 1/132 (0.8%) | 0/53 (0%) | ||
| Viral upper respiratory tract infection | 0/132 (0%) | 1/53 (1.9%) | ||
| Injury, poisoning and procedural complications | ||||
| Alcohol poisoning | 0/132 (0%) | 1/53 (1.9%) | ||
| Arteriovenous fistula thrombosis | 0/132 (0%) | 1/53 (1.9%) | ||
| Citrate toxicity | 1/132 (0.8%) | 0/53 (0%) | ||
| Collapse of lung | 1/132 (0.8%) | 0/53 (0%) | ||
| Device failure | 0/132 (0%) | 1/53 (1.9%) | ||
| Drug toxicity | 1/132 (0.8%) | 0/53 (0%) | ||
| Excoriation | 0/132 (0%) | 1/53 (1.9%) | ||
| Fall | 0/132 (0%) | 1/53 (1.9%) | ||
| Haemolytic transfusion reaction | 1/132 (0.8%) | 0/53 (0%) | ||
| Head injury | 0/132 (0%) | 1/53 (1.9%) | ||
| Incision site pain | 1/132 (0.8%) | 0/53 (0%) | ||
| Jaw fracture | 1/132 (0.8%) | 0/53 (0%) | ||
| Medical device complication | 0/132 (0%) | 1/53 (1.9%) | ||
| Meniscus lesion | 1/132 (0.8%) | 0/53 (0%) | ||
| Overdose | 0/132 (0%) | 1/53 (1.9%) | ||
| Patella fracture | 0/132 (0%) | 1/53 (1.9%) | ||
| Transfusion reaction | 3/132 (2.3%) | 0/53 (0%) | ||
| Vascular graft occlusion | 0/132 (0%) | 1/53 (1.9%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/132 (0.8%) | 1/53 (1.9%) | ||
| Aspartate aminotransferase increased | 1/132 (0.8%) | 1/53 (1.9%) | ||
| Biopsy liver | 1/132 (0.8%) | 0/53 (0%) | ||
| Blood alkaline phosphatase | 1/132 (0.8%) | 0/53 (0%) | ||
| Blood amylase increased | 1/132 (0.8%) | 0/53 (0%) | ||
| Blood bilirubin increased | 1/132 (0.8%) | 0/53 (0%) | ||
| Blood iron increased | 1/132 (0.8%) | 0/53 (0%) | ||
| Lipase increased | 1/132 (0.8%) | 0/53 (0%) | ||
| Oxygen saturation decreased | 1/132 (0.8%) | 0/53 (0%) | ||
| Pregnancy test positive | 1/132 (0.8%) | 0/53 (0%) | ||
| Transaminases increased | 1/132 (0.8%) | 0/53 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 1/132 (0.8%) | 0/53 (0%) | ||
| Dehydration | 4/132 (3%) | 1/53 (1.9%) | ||
| Hyponatraemia | 1/132 (0.8%) | 0/53 (0%) | ||
| Iron overload | 1/132 (0.8%) | 1/53 (1.9%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 3/132 (2.3%) | 2/53 (3.8%) | ||
| Back pain | 6/132 (4.5%) | 5/53 (9.4%) | ||
| Bone pain | 1/132 (0.8%) | 0/53 (0%) | ||
| Bursitis | 1/132 (0.8%) | 0/53 (0%) | ||
| Costochondritis | 0/132 (0%) | 1/53 (1.9%) | ||
| Flank pain | 1/132 (0.8%) | 0/53 (0%) | ||
| Muscular weakness | 1/132 (0.8%) | 0/53 (0%) | ||
| Musculoskeletal pain | 3/132 (2.3%) | 0/53 (0%) | ||
| Osteolysis | 1/132 (0.8%) | 0/53 (0%) | ||
| Osteonecrosis | 4/132 (3%) | 0/53 (0%) | ||
| Pain in extremity | 6/132 (4.5%) | 3/53 (5.7%) | ||
| Rheumatoid arthritis | 0/132 (0%) | 1/53 (1.9%) | ||
| Rotator cuff syndrome | 1/132 (0.8%) | 0/53 (0%) | ||
| Synovial cyst | 1/132 (0.8%) | 0/53 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Chronic myeloid leukaemia | 1/132 (0.8%) | 0/53 (0%) | ||
| Lung neoplasm | 0/132 (0%) | 1/53 (1.9%) | ||
| Nervous system disorders | ||||
| Altered state of consciousness | 1/132 (0.8%) | 0/53 (0%) | ||
| Complex partial seizures | 1/132 (0.8%) | 0/53 (0%) | ||
| Convulsion | 3/132 (2.3%) | 1/53 (1.9%) | ||
| Dizziness | 1/132 (0.8%) | 0/53 (0%) | ||
| Encephalopathy | 1/132 (0.8%) | 0/53 (0%) | ||
| Facial palsy | 1/132 (0.8%) | 0/53 (0%) | ||
| Haemorrhage intracranial | 1/132 (0.8%) | 0/53 (0%) | ||
| Headache | 7/132 (5.3%) | 2/53 (3.8%) | ||
| Hepatic encephalopathy | 1/132 (0.8%) | 0/53 (0%) | ||
| Hypoaesthesia | 2/132 (1.5%) | 0/53 (0%) | ||
| Intraventricular haemorrhage | 1/132 (0.8%) | 2/53 (3.8%) | ||
| Migraine | 2/132 (1.5%) | 0/53 (0%) | ||
| Paraesthesia | 1/132 (0.8%) | 0/53 (0%) | ||
| Syncope | 3/132 (2.3%) | 0/53 (0%) | ||
| Transient ischaemic attack | 3/132 (2.3%) | 0/53 (0%) | ||
| Pregnancy, puerperium and perinatal conditions | ||||
| Abortion spontaneous | 1/132 (0.8%) | 1/53 (1.9%) | ||
| Pregnancy | 3/132 (2.3%) | 1/53 (1.9%) | ||
| Psychiatric disorders | ||||
| Abnormal behaviour | 1/132 (0.8%) | 0/53 (0%) | ||
| Conversion disorder | 1/132 (0.8%) | 0/53 (0%) | ||
| Mental status changes | 1/132 (0.8%) | 0/53 (0%) | ||
| Renal and urinary disorders | ||||
| Enuresis | 1/132 (0.8%) | 0/53 (0%) | ||
| Haematuria | 0/132 (0%) | 1/53 (1.9%) | ||
| Nephropathy toxic | 0/132 (0%) | 1/53 (1.9%) | ||
| Oliguria | 1/132 (0.8%) | 0/53 (0%) | ||
| Renal failure acute | 2/132 (1.5%) | 0/53 (0%) | ||
| Reproductive system and breast disorders | ||||
| Breast swelling | 1/132 (0.8%) | 0/53 (0%) | ||
| Epididymitis | 1/132 (0.8%) | 0/53 (0%) | ||
| Priapism | 3/132 (2.3%) | 1/53 (1.9%) | ||
| Vaginal haemorrhage | 0/132 (0%) | 1/53 (1.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 1/132 (0.8%) | 0/53 (0%) | ||
| Cough | 4/132 (3%) | 0/53 (0%) | ||
| Dyspnoea | 4/132 (3%) | 1/53 (1.9%) | ||
| Epistaxis | 1/132 (0.8%) | 0/53 (0%) | ||
| Lung infiltration | 1/132 (0.8%) | 0/53 (0%) | ||
| Oropharyngeal pain | 1/132 (0.8%) | 0/53 (0%) | ||
| Pleural effusion | 1/132 (0.8%) | 0/53 (0%) | ||
| Pneumonitis | 1/132 (0.8%) | 0/53 (0%) | ||
| Productive cough | 1/132 (0.8%) | 0/53 (0%) | ||
| Pulmonary hypertension | 0/132 (0%) | 2/53 (3.8%) | ||
| Pulmonary thrombosis | 1/132 (0.8%) | 0/53 (0%) | ||
| Respiratory failure | 1/132 (0.8%) | 0/53 (0%) | ||
| Respiratory tract congestion | 1/132 (0.8%) | 0/53 (0%) | ||
| Wheezing | 1/132 (0.8%) | 0/53 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Skin ulcer | 2/132 (1.5%) | 0/53 (0%) | ||
| Swelling face | 1/132 (0.8%) | 0/53 (0%) | ||
| Surgical and medical procedures | ||||
| Catheter placement | 1/132 (0.8%) | 0/53 (0%) | ||
| Catheter removal | 1/132 (0.8%) | 0/53 (0%) | ||
| Central venous catheterisation | 1/132 (0.8%) | 0/53 (0%) | ||
| Cholecystectomy | 1/132 (0.8%) | 0/53 (0%) | ||
| Hip arthroplasty | 1/132 (0.8%) | 0/53 (0%) | ||
| Vascular disorders | ||||
| Haematoma | 1/132 (0.8%) | 0/53 (0%) | ||
| Hypotension | 1/132 (0.8%) | 0/53 (0%) | ||
| Jugular vein distension | 1/132 (0.8%) | 0/53 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| ICL670 | Crossover | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 129/132 (97.7%) | 47/53 (88.7%) | ||
| Blood and lymphatic system disorders | ||||
| Leukocytosis | 4/132 (3%) | 3/53 (5.7%) | ||
| Lymphadenopathy | 8/132 (6.1%) | 2/53 (3.8%) | ||
| Cardiac disorders | ||||
| Tachycardia | 2/132 (1.5%) | 3/53 (5.7%) | ||
| Congenital, familial and genetic disorders | ||||
| Sickle cell anaemia with crisis | 37/132 (28%) | 13/53 (24.5%) | ||
| Ear and labyrinth disorders | ||||
| Ear pain | 8/132 (6.1%) | 3/53 (5.7%) | ||
| Eye disorders | ||||
| Ocular icterus | 11/132 (8.3%) | 6/53 (11.3%) | ||
| Vision blurred | 9/132 (6.8%) | 5/53 (9.4%) | ||
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 9/132 (6.8%) | 2/53 (3.8%) | ||
| Abdominal pain | 32/132 (24.2%) | 13/53 (24.5%) | ||
| Abdominal pain upper | 27/132 (20.5%) | 15/53 (28.3%) | ||
| Constipation | 28/132 (21.2%) | 7/53 (13.2%) | ||
| Diarrhoea | 39/132 (29.5%) | 19/53 (35.8%) | ||
| Dyspepsia | 8/132 (6.1%) | 3/53 (5.7%) | ||
| Gastrooesophageal reflux disease | 2/132 (1.5%) | 3/53 (5.7%) | ||
| Nausea | 52/132 (39.4%) | 19/53 (35.8%) | ||
| Toothache | 9/132 (6.8%) | 4/53 (7.5%) | ||
| Vomiting | 45/132 (34.1%) | 17/53 (32.1%) | ||
| General disorders | ||||
| Asthenia | 7/132 (5.3%) | 1/53 (1.9%) | ||
| Chest pain | 24/132 (18.2%) | 15/53 (28.3%) | ||
| Chills | 9/132 (6.8%) | 4/53 (7.5%) | ||
| Fatigue | 22/132 (16.7%) | 7/53 (13.2%) | ||
| Oedema peripheral | 14/132 (10.6%) | 4/53 (7.5%) | ||
| Pain | 16/132 (12.1%) | 6/53 (11.3%) | ||
| Pyrexia | 45/132 (34.1%) | 22/53 (41.5%) | ||
| Hepatobiliary disorders | ||||
| Jaundice | 6/132 (4.5%) | 3/53 (5.7%) | ||
| Infections and infestations | ||||
| Bronchitis | 8/132 (6.1%) | 1/53 (1.9%) | ||
| Cellulitis | 2/132 (1.5%) | 3/53 (5.7%) | ||
| Ear infection | 9/132 (6.8%) | 1/53 (1.9%) | ||
| Gastroenteritis | 12/132 (9.1%) | 3/53 (5.7%) | ||
| Gastroenteritis viral | 8/132 (6.1%) | 4/53 (7.5%) | ||
| Influenza | 14/132 (10.6%) | 4/53 (7.5%) | ||
| Nasopharyngitis | 37/132 (28%) | 16/53 (30.2%) | ||
| Oral herpes | 8/132 (6.1%) | 1/53 (1.9%) | ||
| Pharyngitis | 12/132 (9.1%) | 4/53 (7.5%) | ||
| Pharyngitis streptococcal | 7/132 (5.3%) | 4/53 (7.5%) | ||
| Pneumonia | 2/132 (1.5%) | 3/53 (5.7%) | ||
| Rhinitis | 9/132 (6.8%) | 0/53 (0%) | ||
| Sinusitis | 17/132 (12.9%) | 5/53 (9.4%) | ||
| Staphylococcal infection | 7/132 (5.3%) | 1/53 (1.9%) | ||
| Tonsillitis | 7/132 (5.3%) | 1/53 (1.9%) | ||
| Upper respiratory tract infection | 43/132 (32.6%) | 19/53 (35.8%) | ||
| Urinary tract infection | 20/132 (15.2%) | 3/53 (5.7%) | ||
| Viral infection | 11/132 (8.3%) | 1/53 (1.9%) | ||
| Injury, poisoning and procedural complications | ||||
| Allergic transfusion reaction | 1/132 (0.8%) | 3/53 (5.7%) | ||
| Excoriation | 8/132 (6.1%) | 0/53 (0%) | ||
| Skin laceration | 4/132 (3%) | 3/53 (5.7%) | ||
| Transfusion reaction | 8/132 (6.1%) | 2/53 (3.8%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 6/132 (4.5%) | 4/53 (7.5%) | ||
| Aspartate aminotransferase increased | 8/132 (6.1%) | 3/53 (5.7%) | ||
| Blood creatinine increased | 12/132 (9.1%) | 4/53 (7.5%) | ||
| Serum ferritin increased | 8/132 (6.1%) | 4/53 (7.5%) | ||
| Transaminases increased | 9/132 (6.8%) | 1/53 (1.9%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 7/132 (5.3%) | 3/53 (5.7%) | ||
| Dehydration | 5/132 (3.8%) | 4/53 (7.5%) | ||
| Vitamin D deficiency | 8/132 (6.1%) | 5/53 (9.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 36/132 (27.3%) | 14/53 (26.4%) | ||
| Back pain | 48/132 (36.4%) | 15/53 (28.3%) | ||
| Bone pain | 9/132 (6.8%) | 0/53 (0%) | ||
| Muscle spasms | 10/132 (7.6%) | 1/53 (1.9%) | ||
| Muscular weakness | 5/132 (3.8%) | 3/53 (5.7%) | ||
| Musculoskeletal pain | 12/132 (9.1%) | 9/53 (17%) | ||
| Myalgia | 6/132 (4.5%) | 4/53 (7.5%) | ||
| Neck pain | 3/132 (2.3%) | 4/53 (7.5%) | ||
| Pain in extremity | 41/132 (31.1%) | 13/53 (24.5%) | ||
| Nervous system disorders | ||||
| Dizziness | 17/132 (12.9%) | 7/53 (13.2%) | ||
| Headache | 61/132 (46.2%) | 30/53 (56.6%) | ||
| Hypoaesthesia | 7/132 (5.3%) | 1/53 (1.9%) | ||
| Migraine | 7/132 (5.3%) | 4/53 (7.5%) | ||
| Psychiatric disorders | ||||
| Anxiety | 7/132 (5.3%) | 3/53 (5.7%) | ||
| Depression | 10/132 (7.6%) | 0/53 (0%) | ||
| Insomnia | 13/132 (9.8%) | 2/53 (3.8%) | ||
| Renal and urinary disorders | ||||
| Chromaturia | 3/132 (2.3%) | 3/53 (5.7%) | ||
| Proteinuria | 7/132 (5.3%) | 0/53 (0%) | ||
| Reproductive system and breast disorders | ||||
| Dysmenorrhoea | 10/132 (7.6%) | 4/53 (7.5%) | ||
| Ovarian cyst | 1/132 (0.8%) | 3/53 (5.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 35/132 (26.5%) | 14/53 (26.4%) | ||
| Dyspnoea | 12/132 (9.1%) | 6/53 (11.3%) | ||
| Epistaxis | 8/132 (6.1%) | 4/53 (7.5%) | ||
| Nasal congestion | 22/132 (16.7%) | 9/53 (17%) | ||
| Oropharyngeal pain | 40/132 (30.3%) | 15/53 (28.3%) | ||
| Rhinitis allergic | 6/132 (4.5%) | 3/53 (5.7%) | ||
| Rhinorrhoea | 9/132 (6.8%) | 4/53 (7.5%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Acne | 5/132 (3.8%) | 3/53 (5.7%) | ||
| Pruritus | 16/132 (12.1%) | 3/53 (5.7%) | ||
| Rash | 21/132 (15.9%) | 9/53 (17%) | ||
| Rash papular | 7/132 (5.3%) | 1/53 (1.9%) | ||
| Urticaria | 9/132 (6.8%) | 4/53 (7.5%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT01090323
Other Study ID Numbers:
- CICL670A0109E1
- EudraCT no. 2004-000597-31
- NCT00171197
First Posted:
Mar 19, 2010
Last Update Posted:
Jun 6, 2011
Last Verified:
May 1, 2011