Carcinoma, Squamous Cell of Head and Neck
Conditions
Brief summary
The trial is designed as a multi-center, open label Phase 2 trial that investigates the efficacy and safety of Sym004 in subjects with squamous cell cancer of the head and neck (SCCHN). Subjects included must have responded to previous anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody-based therapy and subsequently become resistant to that therapy. It is believed that Sym004 has the potential to induce tumor responses and provide a superior treatment option to subjects with advanced SCCHN. Symphogen was the sponsor for planning/conducting and reporting results for this trial.
Interventions
DRUGSym004
Sym004 will be administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.
Sponsors
Symphogen A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis initially or at relapse of SCCHN of the oral cavity, oropharynx, hypopharynx or larynx * Recurrent and/or metastatic SCCHN not amenable to curative treatment with surgery and/or (chemo)radiation * Previous treatment with an anti-EGFR monoclonal antibody (mAb) in the palliative setting either as monotherapy or in combination with chemotherapy or radiotherapy and showing: * Documented clinical benefit or response for at least 8 weeks (PR, CR or SD) on the anti-EGFR mAb-based therapy and * Documented disease progression (verified by computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\] according to RECIST (1.1) during or within 12 weeks following the last administration of anti-EGFR mAb * Accessible tumor for biopsy and subject acceptance of repeat tumor biopsies * Other protocol-defined inclusion criteria could apply
Exclusion criteria
* More than 2 lines of prior chemotherapy in the palliative setting * Expected survival \<12 weeks * Subjects with known brain metastases * Chemotherapy or radiation therapy within 21 days prior to Visit 2 at the exception of palliative radiotherapy for bleeding or pain, which is allowed anytime, if not given on target lesions * Anti-EGFR mAbs within 14 days prior to Visit 2 * Major surgery within 4 weeks prior to Visit 2 and subjects must have recovered from effects of major surgery * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Time | Time from the first infusion of Sym004 until progressive disease or death, assessed up to 24 weeks | The PFS time was defined as the time from first infusion of Sym004 until progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. or death. PD was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The unequivocal progression of existing non-target lesions and the appearance of one or more lesions was also considered progression. Subjects who died without confirmed PD were considered as progressed. Subjects who died or showed PD more than 21 days after last treatment were censored (that is, were considered alive without progression on Day 21 after last treatment). Evaluation was done using Kaplan-Meier estimates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Overall Response | Time from first infusion of Sym004 until disease progression or death, assessed up to 18 months | Duration of overall response was defined as the time from the first time point where measurement criteria are met for CR or PR until first date of recurrence or PD was objectively documented according to RECIST Version 1.1. Duration of overall response was censored at date of last imaging data of measured lesions if no confirmation of recurrence or PD was available. |
| Time to Progression (TTP) | Time from first infusion of Sym04 until disease progression, assessed up to 18 months | The TTP was defined as the time from first infusion of Sym004 until disease progression according to RECIST Version 1.1 criteria. Disease progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The subjects who died without prior assessment of PD were censored for TTP. |
| Overall Survival Time | Time from first infusion of Sym004 until death, assessed up to 18 months | Overall survival time was defined as the time from first infusion of Sym004 until date of death. Subjects who withdraw the consent or lost to follow-up were censored. |
| Number of Subjects With Detectable Biomarkers at Any Visit | Weeks 0 and 4; and 4 weeks after last dose | The biomarkers human papilloma virus (HPV), mutated epidermal growth factor receptor (EGFRvIII), c-MET and human epidermal growth factor receptor (HER) 2, HER3 were analyzed only in tumor cells while EGFR, phosphorylated epidermal growth factor receptor (pEGFR), and Ki-67 were analyzed both in tumor and skin biopsy cells. |
| Area Under the Serum Concentration Curve From Time Zero to 168 Hours (AUC [0-168]) | Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3 | The AUC (0-168h) was estimated by determining the total area under the curve of the concentration versus time curve. |
| Area Under the Serum Concentration Curve From Time Zero to Infinity (AUC [0-inf]) | Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3 | The AUC (0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. |
| Maximum Serum Concentration (Cmax) | Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3 | — |
| Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate) | Time from first infusion of Sym004 until disease progression or death, assessed up to 18 months | Best objective tumor response was defined as the occurrence of complete response (CR), partial response (PR), stable disease (SD), or PD according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Objective response was defined as the occurrence of CR or PR according to RECIST Version 1.1. Disease control was defined as the occurrence of CR, PR or SD according to RECIST Version 1.1. CR: Disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm; PR: At least a 30% decrease in the sum of diameters of all - lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on trial. |
| Clearance (CL) | Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3 | Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. |
| Terminal Half Life (T1/2) | Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3 | The apparent terminal half-life was defined as the time required for the serum concentration of Sym004 to decrease 50% in the final stage of its elimination. |
| Time to Reach Maximum Serum Concentration (Tmax) | Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3 | — |
| Time to Reach Minimum Serum Concentration (Tmin) | Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3 | — |
| Volume of Distribution (Vz) | Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3 | Volume of distribution was defined as the theoretical volume in which the total amount of drug needed to be uniformly distributed to produce the desired serum concentration of a drug. |
| Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation | From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration | An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. |
| Minimum Serum Concentration (Cmin) | Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3 | — |
Countries
Belgium, France, Germany
Participant flow
Recruitment details
First subject (informed consent): 15 July 2011. Last subject completed: 08 October 2012; Clinical data cut-off: 08 October 2012. Subjects randomized at 10 centers in Belgium, France and Germany.
Pre-assignment details
A total of 28 subjects were screened for eligibility, 2 were excluded (mainly non-fulfillment of inclusion or exclusion criteria) and 26 subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Sym004 Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment. | 26 |
| Total | 26 |
Baseline characteristics
| Characteristic | Sym004 |
|---|---|
| Age, Continuous | 62.0 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 26 / 26 |
| serious Total, serious adverse events | 20 / 26 |
Outcome results
Primary
Progression Free Survival (PFS) Time
The PFS time was defined as the time from first infusion of Sym004 until progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. or death. PD was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The unequivocal progression of existing non-target lesions and the appearance of one or more lesions was also considered progression. Subjects who died without confirmed PD were considered as progressed. Subjects who died or showed PD more than 21 days after last treatment were censored (that is, were considered alive without progression on Day 21 after last treatment). Evaluation was done using Kaplan-Meier estimates.
Time frame: Time from the first infusion of Sym004 until progressive disease or death, assessed up to 24 weeks
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sym004 | Progression Free Survival (PFS) Time | 82 days |
Secondary
Area Under the Serum Concentration Curve From Time Zero to 168 Hours (AUC [0-168])
The AUC (0-168h) was estimated by determining the total area under the curve of the concentration versus time curve.
Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sym004 | Area Under the Serum Concentration Curve From Time Zero to 168 Hours (AUC [0-168]) | Week 0 (n=26) | 17574.9 microgram-hour/milliliter | Standard Deviation 5863.6 |
| Sym004 | Area Under the Serum Concentration Curve From Time Zero to 168 Hours (AUC [0-168]) | Week 3 (n=23) | 25690.8 microgram-hour/milliliter | Standard Deviation 14857.1 |
Secondary
Area Under the Serum Concentration Curve From Time Zero to Infinity (AUC [0-inf])
The AUC (0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sym004 | Area Under the Serum Concentration Curve From Time Zero to Infinity (AUC [0-inf]) | Week 0 (n=24) | 24620.8 microgram-hour/milliliter | Standard Deviation 7883.7 |
| Sym004 | Area Under the Serum Concentration Curve From Time Zero to Infinity (AUC [0-inf]) | Week 3 (n=15) | 61655.7 microgram-hour/milliliter | Standard Deviation 22954.9 |
Secondary
Clearance (CL)
Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sym004 | Clearance (CL) | Week 0 (n=24) | 0.55 milliliter/hour/kilogram | Standard Deviation 0.22 |
| Sym004 | Clearance (CL) | Week 3 (n=15) | 0.22 milliliter/hour/kilogram | Standard Deviation 0.08 |
Secondary
Duration of Overall Response
Duration of overall response was defined as the time from the first time point where measurement criteria are met for CR or PR until first date of recurrence or PD was objectively documented according to RECIST Version 1.1. Duration of overall response was censored at date of last imaging data of measured lesions if no confirmation of recurrence or PD was available.
Time frame: Time from first infusion of Sym004 until disease progression or death, assessed up to 18 months
Population: Duration of overall response could not be calculated as no subject showed CR or PR.
Secondary
Maximum Serum Concentration (Cmax)
Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sym004 | Maximum Serum Concentration (Cmax) | Week 0 (n=26) | 248.4 microgram/milliliter | Standard Deviation 82.7 |
| Sym004 | Maximum Serum Concentration (Cmax) | Week 3 (n=23) | 299.8 microgram/milliliter | Standard Deviation 139 |
Secondary
Minimum Serum Concentration (Cmin)
Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sym004 | Minimum Serum Concentration (Cmin) | Week 0 (n=26) | 48.2 microgram/milliliter | Standard Deviation 20.1 |
| Sym004 | Minimum Serum Concentration (Cmin) | Week 3 (n=23) | 93.6 microgram/milliliter | Standard Deviation 45.3 |
Secondary
Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation
An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Time frame: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sym004 | Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation | AEs | 26 Subjects |
| Sym004 | Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation | SAEs | 20 Subjects |
| Sym004 | Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation | AEs Leading to Death | 5 Subjects |
| Sym004 | Number of Subjects With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 6 Subjects |
Secondary
Number of Subjects With Detectable Biomarkers at Any Visit
The biomarkers human papilloma virus (HPV), mutated epidermal growth factor receptor (EGFRvIII), c-MET and human epidermal growth factor receptor (HER) 2, HER3 were analyzed only in tumor cells while EGFR, phosphorylated epidermal growth factor receptor (pEGFR), and Ki-67 were analyzed both in tumor and skin biopsy cells.
Time frame: Weeks 0 and 4; and 4 weeks after last dose
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. n signifies subjects evaluable for specified biomarker type.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Tumor biopsy: HPV (n=19) | 1 Subjects |
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Tumor biopsy: EGFRvIII (n=21) | 0 Subjects |
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Tumor biopsy: cMET (n=19) | 6 Subjects |
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Tumor biopsy: HER2 (n=17) | 0 Subjects |
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Tumor biopsy: HER3 (n=17) | 0 Subjects |
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Skin biopsy: EGFR (n=18) | 0 Subjects |
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Tumor biopsy: EGFR (n=11) | 0 Subjects |
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Tumor biopsy: pEGFR (n=26) | 0 Subjects |
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Skin biopsy: pEGFR (n=26) | 0 Subjects |
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Skin biopsy: Increase in Ki67 (n=18) | 9 Subjects |
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Skin biopsy: Decrease in Ki67 (n=18) | 9 Subjects |
| Sym004 | Number of Subjects With Detectable Biomarkers at Any Visit | Tumor biopsy: Decrease in Ki67 (n=11) | 4 Subjects |
Secondary
Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate)
Best objective tumor response was defined as the occurrence of complete response (CR), partial response (PR), stable disease (SD), or PD according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Objective response was defined as the occurrence of CR or PR according to RECIST Version 1.1. Disease control was defined as the occurrence of CR, PR or SD according to RECIST Version 1.1. CR: Disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm; PR: At least a 30% decrease in the sum of diameters of all - lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on trial.
Time frame: Time from first infusion of Sym004 until disease progression or death, assessed up to 18 months
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sym004 | Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate) | CR | 0 Percentage of subjects |
| Sym004 | Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate) | PR | 0 Percentage of subjects |
| Sym004 | Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate) | SD | 50.0 Percentage of subjects |
| Sym004 | Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate) | PD | 23.1 Percentage of subjects |
Secondary
Overall Survival Time
Overall survival time was defined as the time from first infusion of Sym004 until date of death. Subjects who withdraw the consent or lost to follow-up were censored.
Time frame: Time from first infusion of Sym004 until death, assessed up to 18 months
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sym004 | Overall Survival Time | 156 days |
Secondary
Terminal Half Life (T1/2)
The apparent terminal half-life was defined as the time required for the serum concentration of Sym004 to decrease 50% in the final stage of its elimination.
Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sym004 | Terminal Half Life (T1/2) | Week 0 (n=24) | 89.1 hour | Standard Deviation 26.5 |
| Sym004 | Terminal Half Life (T1/2) | Week 3 (n=15) | 140.7 hour | Standard Deviation 37.6 |
Secondary
Time to Progression (TTP)
The TTP was defined as the time from first infusion of Sym004 until disease progression according to RECIST Version 1.1 criteria. Disease progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The subjects who died without prior assessment of PD were censored for TTP.
Time frame: Time from first infusion of Sym04 until disease progression, assessed up to 18 months
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sym004 | Time to Progression (TTP) | 85 days |
Secondary
Time to Reach Maximum Serum Concentration (Tmax)
Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sym004 | Time to Reach Maximum Serum Concentration (Tmax) | Week 0 (n=26) | 6.0 hour | Standard Deviation 5.4 |
| Sym004 | Time to Reach Maximum Serum Concentration (Tmax) | Week 3 (n=23) | 4.7 hour | Standard Deviation 3.4 |
Secondary
Time to Reach Minimum Serum Concentration (Tmin)
Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sym004 | Time to Reach Minimum Serum Concentration (Tmin) | Week 0 (n=26) | 163.5 hour | Standard Deviation 22.9 |
| Sym004 | Time to Reach Minimum Serum Concentration (Tmin) | Week 3 (n=23) | 58.4 hour | Standard Deviation 81.8 |
Secondary
Volume of Distribution (Vz)
Volume of distribution was defined as the theoretical volume in which the total amount of drug needed to be uniformly distributed to produce the desired serum concentration of a drug.
Time frame: Pre-treatment, 1, 2, 4, 8, 24, and 48 hours post-infusion at Week 0 and Week 3
Population: The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sym004 | Volume of Distribution (Vz) | Week 0 (n=24) | 67.0 milliliter/kilogram | Standard Deviation 23.2 |
| Sym004 | Volume of Distribution (Vz) | Week 3 (n=15) | 40.9 milliliter/kilogram | Standard Deviation 10.3 |