Trial Outcomes & Findings for N2007-01: Ultratrace™ Iobenguane I 131 in Patients With Relapsed/Refractory High-Risk Neuroblastoma (NCT NCT00659984)
NCT ID: NCT00659984
Last Updated: 2017-10-04
Results Overview
The maximum tolerated dose (MTD) was defined as the dose immediately below the level at which dose escalation would be stopped due to dose limiting toxicities (DLTs). Once the MTD was reached, an additional 3 patients were to be treated at that dose level, for a total of 6 patients at that planned dose level. DLTs were defined as any of the events that are possibly, probably or definitely attributable to UltratraceTM iobenguane I 131. The MTD was supposed to be the highest dose tested at which fewer than 1/3 of pts experience a DLT when 6 patients have been treated at the MTD but the dosimetry results indicated that the maximal dosage allowed to normal organs would be exceeded if the highest planned dose (21.0 mCi/kg) was administered, so the highest dose administered in the study was 18.6 mCi/kg .
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
15 participants
Primary outcome timeframe
Day 60 +/-10 or Engraftment, whichever comes first
Results posted on
2017-10-04
Participant Flow
Participant milestones
| Measure |
Ultratrace™ Iobenguane I 131
Eligible patients received a diagnostic imaging dose of Ultratrace™ Iobenguane I 131 within 7 days (d) of enrollment, followed by 3 dosimetry scans over 3-6 days. For the imaging dose, 0.1 mCi/kg (3.7 MBq/kg), at a min dose of 1 mCi (37 MBq) but not to exceed 5 mCi (185 MBq) of Ultratrace™ Iobenguane I 131 was administered 7-28 d prior to the therapeutic dose on Day 0. If the imaging dose demonstrated NL biodistribution/tumor uptake, pts received a therapeutic dose within 7-28 d of the imaging dose followed by a single imaging scan on Day 7 post therapy.
Therapeutic dosing was to begin at 12.0 mCi/kg and escalate to 15.0, 18.0, and 21.0 mCi/kg until the MTD was established or the 21.0 mCi/kg dose level was reached. Based on actual doses administered, pts were grouped into 3 mean dose groups: 11.2, 15.5, and 18.2 mCi/kg.
The dosimetry dose was administered over 1-3 mins by injection; the therapeutic dose was diluted in up to 25 mL normal saline and infused over 30 to 60 mins.
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
COMPLETED
|
14
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Ultratrace™ Iobenguane I 131
Eligible patients received a diagnostic imaging dose of Ultratrace™ Iobenguane I 131 within 7 days (d) of enrollment, followed by 3 dosimetry scans over 3-6 days. For the imaging dose, 0.1 mCi/kg (3.7 MBq/kg), at a min dose of 1 mCi (37 MBq) but not to exceed 5 mCi (185 MBq) of Ultratrace™ Iobenguane I 131 was administered 7-28 d prior to the therapeutic dose on Day 0. If the imaging dose demonstrated NL biodistribution/tumor uptake, pts received a therapeutic dose within 7-28 d of the imaging dose followed by a single imaging scan on Day 7 post therapy.
Therapeutic dosing was to begin at 12.0 mCi/kg and escalate to 15.0, 18.0, and 21.0 mCi/kg until the MTD was established or the 21.0 mCi/kg dose level was reached. Based on actual doses administered, pts were grouped into 3 mean dose groups: 11.2, 15.5, and 18.2 mCi/kg.
The dosimetry dose was administered over 1-3 mins by injection; the therapeutic dose was diluted in up to 25 mL normal saline and infused over 30 to 60 mins.
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
N2007-01: Ultratrace™ Iobenguane I 131 in Patients With Relapsed/Refractory High-Risk Neuroblastoma
Baseline characteristics by cohort
| Measure |
Ultratrace™ Iobenguane I 131
n=15 Participants
Eligible patients received a diagnostic imaging dose of Ultratrace™ Iobenguane I 131 (1-5 mCi) within 7 days of study enrollment, followed by three dosimetry scans over 3-6 days. If the imaging dose demonstrated normal biodistribution and tumor uptake, then the patient received a therapeutic dose within 7-28 days of the diagnostic imaging dose, followed by a single imaging scan on Day 7 post therapy. Therapeutic dosing began at 12.0 mCi/kg and escalated to 15.0, 18.0, and 21.0 mCi/kg until the MTD was established or the 21.0 mCi/kg dose level was reached. The dosimetry dose was administered over a period of 1-3 minutes by injection; the therapeutic dose was diluted in up to 25 mL normal saline and infused intravenously over 30 to 60 minutes.
|
|---|---|
|
Age, Continuous
|
8 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 60 +/-10 or Engraftment, whichever comes firstPopulation: A total of 15 patients underwent dosimetry (received a single imaging dose of Ultratrace™ Iobenguane I 131 injection) and all 15 patients later received a single therapeutic dose of Ultratrace™ Iobenguane I 131.
The maximum tolerated dose (MTD) was defined as the dose immediately below the level at which dose escalation would be stopped due to dose limiting toxicities (DLTs). Once the MTD was reached, an additional 3 patients were to be treated at that dose level, for a total of 6 patients at that planned dose level. DLTs were defined as any of the events that are possibly, probably or definitely attributable to UltratraceTM iobenguane I 131. The MTD was supposed to be the highest dose tested at which fewer than 1/3 of pts experience a DLT when 6 patients have been treated at the MTD but the dosimetry results indicated that the maximal dosage allowed to normal organs would be exceeded if the highest planned dose (21.0 mCi/kg) was administered, so the highest dose administered in the study was 18.6 mCi/kg .
Outcome measures
| Measure |
Ultratrace™ Iobenguane I 131
n=15 Participants
Following therapeutic dosing at the 12.0, 15.0, and 18.0 mCi/kg cohorts, 4 patients who were to receive the 21.0 mCi/kg therapeutic dose were required to have their planned dose reduced below the dose that was calculated based on the patient's dosimetry results, in order to meet the protocol guidelines for maximal dosage allowed to normal organs described above. Because of the differences between the planned and actual therapeutic doses that were administered to several patients, patients were grouped and the study data were presented and analyzed by actual doses rather than by the planned dose cohorts of 12.0, 15.0, 18.0, and 21.0 mCi/kg. Based on the actual doses administered, patients were grouped into 3 dose groups of 6, 3, and 6 patients, according to the mean doses of the groups, which were 11.2, 15.5, and 18.2 mCi/kg, respectively.
|
15.5 mCi Group
15.5 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
18.2 mCi Group
18.2 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
|---|---|---|---|
|
Maximum Tolerated Dose
|
18.6 mCi/kg
|
—
|
—
|
SECONDARY outcome
Timeframe: From the time of signed informed consent until Day 60 or until the end of therapy evaluation is completed (whichever comes first).Population: A total of 15 patients underwent dosimetry (received a single imaging dose of Ultratrace™ Iobenguane I 131 injection) and all 15 patients later received a single therapeutic dose of Ultratrace™ Iobenguane I 131.
Dose limiting toxicities include treatment emergent adverse events (TEAEs) that were possibly, probably, or definitely related to Ultratrace™ Iobenguane I 131.
Outcome measures
| Measure |
Ultratrace™ Iobenguane I 131
n=6 Participants
Following therapeutic dosing at the 12.0, 15.0, and 18.0 mCi/kg cohorts, 4 patients who were to receive the 21.0 mCi/kg therapeutic dose were required to have their planned dose reduced below the dose that was calculated based on the patient's dosimetry results, in order to meet the protocol guidelines for maximal dosage allowed to normal organs described above. Because of the differences between the planned and actual therapeutic doses that were administered to several patients, patients were grouped and the study data were presented and analyzed by actual doses rather than by the planned dose cohorts of 12.0, 15.0, 18.0, and 21.0 mCi/kg. Based on the actual doses administered, patients were grouped into 3 dose groups of 6, 3, and 6 patients, according to the mean doses of the groups, which were 11.2, 15.5, and 18.2 mCi/kg, respectively.
|
15.5 mCi Group
n=3 Participants
15.5 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
18.2 mCi Group
n=6 Participants
18.2 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
|---|---|---|---|
|
Dose Limiting Toxicities
|
0 number of DLTs
|
0 number of DLTs
|
0 number of DLTs
|
SECONDARY outcome
Timeframe: Day 5 post Dosimetric DosePopulation: A total of 15 patients underwent dosimetry (received a single imaging dose of Ultratrace™ Iobenguane I 131 injection).
The dosimetric endpoint was to estimate radiation absorbed doses to measurable lesions and to a standard set of normal organs following an imaging dose of 0.1 mCi/kg Ultratrace™ Iobenguane I 131. Biodistribution was assessed by determination of total body residence (TBR) time and by visual examination of whole body camera images. 3 timepoints were used, the 1st image was taken within 1hr after the imaging dose, the 2nd image was taken at \~24hr after imaging dose, the 3rd image was taken 2-5d after imaging dose. Whole body radiation absorbed dose estimates \& kidney, liver, and lung were calculated using the Medical Internal Radiation Dose (MIRD) schema.TBR time is derived from time integration of curve-fitted injected activity across all 3 timepoints when the isotope is emitting radiation.Three points are sampled to estimate a singular value for each organ and tissue according to the commonly used methods of the Society of Nuclear Medicine and Molecular Imaging Committee on MIRD.
Outcome measures
| Measure |
Ultratrace™ Iobenguane I 131
n=15 Participants
Following therapeutic dosing at the 12.0, 15.0, and 18.0 mCi/kg cohorts, 4 patients who were to receive the 21.0 mCi/kg therapeutic dose were required to have their planned dose reduced below the dose that was calculated based on the patient's dosimetry results, in order to meet the protocol guidelines for maximal dosage allowed to normal organs described above. Because of the differences between the planned and actual therapeutic doses that were administered to several patients, patients were grouped and the study data were presented and analyzed by actual doses rather than by the planned dose cohorts of 12.0, 15.0, 18.0, and 21.0 mCi/kg. Based on the actual doses administered, patients were grouped into 3 dose groups of 6, 3, and 6 patients, according to the mean doses of the groups, which were 11.2, 15.5, and 18.2 mCi/kg, respectively.
|
15.5 mCi Group
15.5 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
18.2 mCi Group
18.2 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
|---|---|---|---|
|
Dosimetric Estimation of Radiation Absorbed Doses to Measurable Lesions
Kidney
|
16.7 Gy
Standard Deviation 5.2
|
—
|
—
|
|
Dosimetric Estimation of Radiation Absorbed Doses to Measurable Lesions
Liver
|
12.7 Gy
Standard Deviation 4.1
|
—
|
—
|
|
Dosimetric Estimation of Radiation Absorbed Doses to Measurable Lesions
Lungs
|
11.1 Gy
Standard Deviation 2.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 60 +/- 10 days post Therapeutic DosePopulation: The evaluable population (which excludes non-evaluable responses) contains one patient less than the full ITT population.
The International Neuroblastoma Response Criteria (INRC) were utilized as a basis for the overall response criteria, which incorporated responses in MIBG positive lesions,bone marrow disease, and CT/MRI lesions that met NANT-modified RECIST criteria. Efficacy success was defined as the proportion of pts who were successful overall \[i.e., achieving a Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR)\] determined by independent reviewers. CR = Disappearance of all target lesions, homovanillic acid/ vanillylmandelic acid (HVA/VMA) normal (NL); VGPR = \> 90% decr of disease for CT/MRI target lesions, all pre-existing bone lesions with CR by MIBG; MIBG scan can be SD/CR in soft tissue lesions. CR in bone marrow, no new tumor sites, and NL HVA/VMA.; PR = At least 30% decr in disease measurement for CT/MRI target lesions. Bone marrow with CR, MIBG with either PR/CR in bone lesions, MIBG may be SD /CR in soft tissue lesions, and HVA/VMA may still be elevated.
Outcome measures
| Measure |
Ultratrace™ Iobenguane I 131
n=14 Participants
Following therapeutic dosing at the 12.0, 15.0, and 18.0 mCi/kg cohorts, 4 patients who were to receive the 21.0 mCi/kg therapeutic dose were required to have their planned dose reduced below the dose that was calculated based on the patient's dosimetry results, in order to meet the protocol guidelines for maximal dosage allowed to normal organs described above. Because of the differences between the planned and actual therapeutic doses that were administered to several patients, patients were grouped and the study data were presented and analyzed by actual doses rather than by the planned dose cohorts of 12.0, 15.0, 18.0, and 21.0 mCi/kg. Based on the actual doses administered, patients were grouped into 3 dose groups of 6, 3, and 6 patients, according to the mean doses of the groups, which were 11.2, 15.5, and 18.2 mCi/kg, respectively.
|
15.5 mCi Group
15.5 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
18.2 mCi Group
18.2 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
|---|---|---|---|
|
Overall Objective Tumor Response Post Therapeutic Treatment
|
0.29 proportion of evaluable population
Interval 0.01 to 0.56
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 60 +/- 10 days post Therapeutic DosePopulation: The evaluable population (which excludes non-evaluable responses) contains one patient less than the full ITT population.
Measurable disease was defined for a conventional CT scan by the presence of at least one lesion that could be accurately measured in at least one dimension with the longest diameter at least 20 mm by Independent Review. Efficacy success was defined as a patient achieving a Complete Response (CR)=disappearance of all target and non-target CT/MRI lesions; or, Very Good Partial Response (VGPR)=greater than 90% decrease of the disease measurement for CT/MRI lesions, taking as reference the disease measurement done to confirm measurement disease at study entry. Non-target CT/MRI lesions stable to smaller in size; or, Partial Response (PR)=at least 30% decrease in the disease measurement for CT/MRI lesions, taking as reference the disease measurement done to confirm measurable disease at study entry. Non-target CT/MRI lesions stable to smaller in size.
Outcome measures
| Measure |
Ultratrace™ Iobenguane I 131
n=14 Participants
Following therapeutic dosing at the 12.0, 15.0, and 18.0 mCi/kg cohorts, 4 patients who were to receive the 21.0 mCi/kg therapeutic dose were required to have their planned dose reduced below the dose that was calculated based on the patient's dosimetry results, in order to meet the protocol guidelines for maximal dosage allowed to normal organs described above. Because of the differences between the planned and actual therapeutic doses that were administered to several patients, patients were grouped and the study data were presented and analyzed by actual doses rather than by the planned dose cohorts of 12.0, 15.0, 18.0, and 21.0 mCi/kg. Based on the actual doses administered, patients were grouped into 3 dose groups of 6, 3, and 6 patients, according to the mean doses of the groups, which were 11.2, 15.5, and 18.2 mCi/kg, respectively.
|
15.5 mCi Group
15.5 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
18.2 mCi Group
18.2 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
|---|---|---|---|
|
Tumor Response in CT/MRI Lesions Post Therapeutic Treatment
|
21 percentage of evaluable population
Interval 0.0 to 46.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 60 +/- 10 days post Therapeutic DosePopulation: Self reported PedsQL™ scores were obtained for 9 patients in the ITT population (n=15) at baseline (prior to the start of the Ultratrace™ Iobenguane I 131 imaging studies) and at the end of therapy (60 ±10 days post treatment).
Patients (aged 5-18) and parents (of patients aged 2-18) were asked to complete the 23-item Pediatric Quality of Life InventoryTM (PedsQLTM). PedsQLTM consists of 4 scales (physical, emotional, social, school functioning) which are then averaged into an overall summary score (scale: 0-100 with 0 representing the worst possible Quality of Life overall summary score and 100 representing the best possible Quality of Life overall summary score). The mean difference between the post treatment overall summary score and the baseline overall summary score is reported.
Outcome measures
| Measure |
Ultratrace™ Iobenguane I 131
n=9 Participants
Following therapeutic dosing at the 12.0, 15.0, and 18.0 mCi/kg cohorts, 4 patients who were to receive the 21.0 mCi/kg therapeutic dose were required to have their planned dose reduced below the dose that was calculated based on the patient's dosimetry results, in order to meet the protocol guidelines for maximal dosage allowed to normal organs described above. Because of the differences between the planned and actual therapeutic doses that were administered to several patients, patients were grouped and the study data were presented and analyzed by actual doses rather than by the planned dose cohorts of 12.0, 15.0, 18.0, and 21.0 mCi/kg. Based on the actual doses administered, patients were grouped into 3 dose groups of 6, 3, and 6 patients, according to the mean doses of the groups, which were 11.2, 15.5, and 18.2 mCi/kg, respectively.
|
15.5 mCi Group
15.5 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
18.2 mCi Group
18.2 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
|
|---|---|---|---|
|
Quality of Life
|
5.2 units on a scale
Standard Deviation 11.27
|
—
|
—
|
Adverse Events
Ultratrace™ Iobenguane I 131
Serious events: 5 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ultratrace™ Iobenguane I 131
n=15 participants at risk
Eligible patients received a diagnostic imaging dose of Ultratrace™ Iobenguane I 131 (1-5 mCi) within 7 days of study enrollment, followed by three dosimetry scans over 3-6 days. If the imaging dose demonstrated normal biodistribution and tumor uptake, then the patient received a therapeutic dose within 7-28 days of the diagnostic imaging dose, followed by a single imaging scan on Day 7 post therapy. Mean therapeutic dosing groups were 11.2 mCi/kg, 15.5 nCi/kg and 18.2 mCi/kg. The dosimetry dose was administered over a period of 1-3 minutes by injection; the therapeutic dose was diluted in up to 25 mL normal saline and infused intravenously over 30 to 60 minutes.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
13.3%
2/15 • Number of events 2 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Infections and infestations
Upper respiratory tract infection
|
6.7%
1/15 • Number of events 1 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Infections and infestations
Infection
|
6.7%
1/15 • Number of events 1 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Infections and infestations
Bacteremia
|
6.7%
1/15 • Number of events 1 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
General disorders
Disease progression
|
6.7%
1/15 • Number of events 1 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Infections and infestations
Neutropenia infection
|
6.7%
1/15 • Number of events 1 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
Other adverse events
| Measure |
Ultratrace™ Iobenguane I 131
n=15 participants at risk
Eligible patients received a diagnostic imaging dose of Ultratrace™ Iobenguane I 131 (1-5 mCi) within 7 days of study enrollment, followed by three dosimetry scans over 3-6 days. If the imaging dose demonstrated normal biodistribution and tumor uptake, then the patient received a therapeutic dose within 7-28 days of the diagnostic imaging dose, followed by a single imaging scan on Day 7 post therapy. Mean therapeutic dosing groups were 11.2 mCi/kg, 15.5 nCi/kg and 18.2 mCi/kg. The dosimetry dose was administered over a period of 1-3 minutes by injection; the therapeutic dose was diluted in up to 25 mL normal saline and infused intravenously over 30 to 60 minutes.
|
|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
100.0%
15/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
100.0%
15/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Blood and lymphatic system disorders
Neutropenia
|
93.3%
14/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
53.3%
8/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Investigations
Aspartate aminotransferase increased
|
80.0%
12/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Investigations
Hemoglobin decreased
|
73.3%
11/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Investigations
Alanine aminotransferase increased
|
60.0%
9/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Investigations
Activated partial thromboplastin time prolonged
|
20.0%
3/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Investigations
Blood bilirubin increased
|
20.0%
3/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Investigations
Weight decreased
|
20.0%
3/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Gastrointestinal disorders
Nausea
|
60.0%
9/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Gastrointestinal disorders
Vomiting
|
40.0%
6/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Gastrointestinal disorders
Diarrhoea
|
26.7%
4/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Gastrointestinal disorders
Salivary gland pain
|
26.7%
4/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Gastrointestinal disorders
Salivary gland enlargement
|
20.0%
3/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Gastrointestinal disorders
Abdominal pain
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Gastrointestinal disorders
Constipation
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Gastrointestinal disorders
Dry mouth
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Metabolism and nutrition disorders
Anorexia
|
26.7%
4/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
20.0%
3/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
20.0%
3/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
General disorders
Pyrexia
|
33.3%
5/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
General disorders
Fatigue
|
20.0%
3/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
General disorders
Oedema peripheral
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Infections and infestations
Candidiasis
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Nervous system disorders
Headache
|
26.7%
4/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Nervous system disorders
Dysgeusia
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Renal and urinary disorders
Bladder spasm
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
|
Vascular disorders
Hypertension
|
13.3%
2/15 • From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60