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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-003722-84 | EudraCT Number | EudraCT |
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Investigate the pharmacokinetics, safety and tolerability of BI695501 and to establish pharmacokinetic similarity of BI 695501 to adalimumab.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 695501 | Experimental | Subject to receive one subcutaneous (s.c.) injection from a prefilled syringe containing BI 695501 |
|
| adalimumab-EU source | Active Comparator | Subject to receive one subcutaneous (s.c.) injection from a prefilled syringe containing adalimumab-EU source |
|
| adalimumab-US source | Active Comparator | Subject to receive one subcutaneous (s.c.) injection from a prefilled syringe containing adalimumab-US source |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 695501 | Drug | BI 695501 single s.c. injection |
| |
| adalimumab-EU source |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration Time Curve (AUC) From Time Zero to Infinity (AUC 0-∞) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to infinity (AUC 0-∞) of BI 695501, US-licensed Humira® or EU-approved Humira®. Abbreviation used: Pharmacokinetics (PK). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. |
| Area Under the Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC0-tz) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve from time zero to last measurable concentration (AUC0-tz) of BI 695501, US-licensed Humira® or EU-approved Humira®. | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. |
| Maximum Concentration (Cmax) of BI 695501, US-licensed Humira® or EU-approved Humira® | Maximum concentration (Cmax) of BI 695501, US-licensed Humira® or EU-approved Humira®. | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. |
| Measure | Description | Time Frame |
|---|---|---|
| AUC (0-168) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 168 hours post dose (AUC 0-168) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168 hours post dosing |
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Inclusion criteria:
Healthy males according to the following criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1297.8.1001 Boehringer Ingelheim Investigational Site | Antwerp | Belgium | ||||
| 1297.8.2001 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33263165 | Derived | Huizinga TWJ, Torii Y, Muniz R. Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity. Rheumatol Ther. 2021 Mar;8(1):41-61. doi: 10.1007/s40744-020-00259-8. Epub 2020 Dec 1. | |
| 32363771 | Derived | Kang J, Eudy-Byrne RJ, Mondick J, Knebel W, Jayadeva G, Liesenfeld KH. Population pharmacokinetics of adalimumab biosimilar adalimumab-adbm and reference product in healthy subjects and patients with rheumatoid arthritis to assess pharmacokinetic similarity. Br J Clin Pharmacol. 2020 Nov;86(11):2274-2285. doi: 10.1111/bcp.14330. Epub 2020 Jun 11. |
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All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that they (the subject) met all strictly implemented inclusion/exclusion criteria. Subjects were not randomised to trial treatment if any one of the specific entry criteria were violated.
In this trial 324 healthy subjects were randomized into 3 arms.
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| ID | Title | Description |
|---|---|---|
| FG000 | BI 695501 | Subject to receive a single subcutaneous (s.c.) injection from a prefilled syringe containing 40 milligram (mg)/0.8 millilitre (mL) BI 695501 solution. |
| FG001 | US-licensed Humira® | Subject to receive a single subcutaneous (s.c.) injection from a prefilled syringe containing 40 mg/0.8 mL US-licensed Humira® |
| FG002 | EU-approved Humira® | Subject to receive a single subcutaneous (s.c.) injection from a prefilled syringe containing 40 mg/0.8 mL European Union (EU)-approved Humira®. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The safety analysis set consisted of all subjects who received the single dose of trial medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | BI 695501 | single s.c. injection 40 mg/0.8 mL BI 695501 solution. |
| BG001 | US-licensed Humira® | single s.c. injection 40 mg/0.8 mL US-licensed Humira® |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration Time Curve (AUC) From Time Zero to Infinity (AUC 0-∞) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to infinity (AUC 0-∞) of BI 695501, US-licensed Humira® or EU-approved Humira®. Abbreviation used: Pharmacokinetics (PK). | PK analysis set consisted of all randomized subjects who received the single dose of trial medication (BI 695501, US-licensed - or EU-approved Humira®), had at least one evaluable primary PK endpoint and were without important protocol deviations or violations thought to significantly affect the PK of BI 695501, US-licensed - or EU-approved Humira® | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram (µg)*hour (h)/millilitre (mL) | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. |
|
Day 1 (first administration of trial medication) until day 71
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BI 695501 | single s.c. injection 40 mg/0.8 mL BI 695501 solution. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MEDDRA 17.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MEDDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| C000632724 | BI 695501 |
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| Drug |
adalimumab-EU source single s.c. injection |
|
| adalimumab-US source | Drug | adalimumab-US source single s.c. injection. |
|
| AUC (0-312) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 312 hours post dose (AUC 0-312) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312 hours post dosing |
| AUC (0-480) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 480 hours post dose (AUC 0-480) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480 hours post dosing |
| AUC (0-648) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 648 hours post dose (AUC 0-648) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648 hours post dosing |
| AUC (0-1032) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 1032 hours post dose (AUC 0-1032) of BI 695501, US-licensed Humira® or EU-approved Humira® PK is the abbreviation for Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032 hours post dosing |
| AUC 0-∞,Obs of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to infinity (AUC 0-∞) based on the last observed concentration at time of last measureable concentration (tz) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation of Pharmacokinetic(s). | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. |
| Number (Proportion) of Subjects With Drug Related Adverse Events | All events with an onset after the first administration of the trial medication up to a period of 70 days after the last administration of the trial medication (i.e., end of the REP) was assigned to the treatment phase for evaluation and was defined as a treatment-emergent AE (TEAE). A treatment-related AE was defined as any TEAE assessed by the investigator as related to the trial medication. All safety data were displayed and analyzed using descriptive statistical methods. No formal inferential analyses were planned for safety comparisons. Tabulations of frequencies and proportions, as appropriate were used for the evaluation of categorical (qualitative) data, and tabulations of descriptive statistics were used to analyze continuous (quantitative) data. | Day 1 through Day 71 |
| Auckland |
| New Zealand |
| 1297.8.2002 Boehringer Ingelheim Investigational Site | Christchurch | New Zealand |
| 27813422 | Derived | Wynne C, Altendorfer M, Sonderegger I, Gheyle L, Ellis-Pegler R, Buschke S, Lang B, Assudani D, Athalye S, Czeloth N. Bioequivalence, safety and immunogenicity of BI 695501, an adalimumab biosimilar candidate, compared with the reference biologic in a randomized, double-blind, active comparator phase I clinical study (VOLTAIRE(R)-PK) in healthy subjects. Expert Opin Investig Drugs. 2016 Dec;25(12):1361-1370. doi: 10.1080/13543784.2016.1255724. |
| BG002 | EU-approved Humira® | single s.c. injection 40 mg/0.8 mL EU-approved Humira® |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
single s.c. injection 40 mg/0.8 mL BI 695501 solution. |
| OG001 | US-licensed Humira® | single s.c. injection 40 mg/0.8 mL US-licensed Humira® |
| OG002 | EU-approved Humira® | single s.c. injection 40 mg/0.8 mL EU-approved Humira® |
|
|
|
| Primary | Area Under the Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC0-tz) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve from time zero to last measurable concentration (AUC0-tz) of BI 695501, US-licensed Humira® or EU-approved Humira®. | The PK analysis set. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg*h/mL | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. |
|
|
|
|
| Primary | Maximum Concentration (Cmax) of BI 695501, US-licensed Humira® or EU-approved Humira® | Maximum concentration (Cmax) of BI 695501, US-licensed Humira® or EU-approved Humira®. | The PK analysis set. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. |
|
|
|
|
| Secondary | AUC (0-168) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 168 hours post dose (AUC 0-168) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | The PK analysis set. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg*h/mL | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168 hours post dosing |
|
|
|
|
| Secondary | AUC (0-312) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 312 hours post dose (AUC 0-312) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | The PK analysis set. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg*h/mL | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312 hours post dosing |
|
|
|
|
| Secondary | AUC (0-480) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 480 hours post dose (AUC 0-480) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | The PK analysis set. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg*h/mL | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480 hours post dosing |
|
|
|
|
| Secondary | AUC (0-648) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 648 hours post dose (AUC 0-648) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation for Pharmacokinetic(s). | The PK analysis set. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg*h/mL | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648 hours post dosing |
|
|
|
|
| Secondary | AUC (0-1032) of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to 1032 hours post dose (AUC 0-1032) of BI 695501, US-licensed Humira® or EU-approved Humira® PK is the abbreviation for Pharmacokinetic(s). | The PK analysis set. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg*h/mL | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032 hours post dosing |
|
|
|
|
| Secondary | AUC 0-∞,Obs of BI 695501, US-licensed Humira® or EU-approved Humira® | Area under the concentration time curve (AUC) from time zero to infinity (AUC 0-∞) based on the last observed concentration at time of last measureable concentration (tz) of BI 695501, US-licensed Humira® or EU-approved Humira®. PK is the abbreviation of Pharmacokinetic(s). | The PK analysis set. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg*h/mL | at -1 hour (h) (pre dosing) and 1h, 4, 8, 12, 24, 48, 72, 84, 96, 108, 120, 132, 144, 168, 192, 240, 312, 480, 648, 1032, 1320 h post dosing and on day 71 post dosing. |
|
|
|
|
| Secondary | Number (Proportion) of Subjects With Drug Related Adverse Events | All events with an onset after the first administration of the trial medication up to a period of 70 days after the last administration of the trial medication (i.e., end of the REP) was assigned to the treatment phase for evaluation and was defined as a treatment-emergent AE (TEAE). A treatment-related AE was defined as any TEAE assessed by the investigator as related to the trial medication. All safety data were displayed and analyzed using descriptive statistical methods. No formal inferential analyses were planned for safety comparisons. Tabulations of frequencies and proportions, as appropriate were used for the evaluation of categorical (qualitative) data, and tabulations of descriptive statistics were used to analyze continuous (quantitative) data. | The safety analysis set consisted of all subjects who received the single dose of trial medication (BI 695501, US-licensed Humira® or EU-approved Humira®). | Posted | Number | participants | Day 1 through Day 71 |
|
|
|
| 3 |
| 108 |
| 51 |
| 108 |
| EG001 | US-licensed Humira® | single s.c. injection 40 mg/0.8 mL US-licensed Humira® | 3 | 108 | 52 | 108 |
| EG002 | EU-approved Humira® | single s.c. injection 40 mg/0.8 mL EU-approved Humira® | 2 | 108 | 51 | 108 |
| Appendicitis | Infections and infestations | MEDDRA 17.0 | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | MEDDRA 17.0 | Systematic Assessment |
|
| Concussion | Injury, poisoning and procedural complications | MEDDRA 17.0 | Systematic Assessment |
|
| Hand fracture | Injury, poisoning and procedural complications | MEDDRA 17.0 | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MEDDRA 17.0 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MEDDRA 17.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MEDDRA 17.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MEDDRA 17.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MEDDRA 17.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MEDDRA 17.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MEDDRA 17.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MEDDRA 17.0 | Systematic Assessment |
|
Other - Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| ratio of the geometric means | 99.93 | 2-Sided | 90 | 92.15 | 108.37 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | PK similarity of the two treatments was to be concluded if the 90% CI for the ratio of adjusted geometric means was within 80.00 - 125.00 %. |
| ratio of the geometric means | 93.66 | 2-Sided | 90 | 86.76 | 101.11 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | PK similarity of the two treatments was to be concluded if the 90% CI for the ratio of adjusted geometric means was within 80.00 - 125.00 %. |
| ratio of the geometric means | 96.39 | 2-Sided | 90 | 91.06 | 102.03 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | PK similarity of the two treatments was to be concluded if the 90% CI for the ratio of adjusted geometric means was within 80.00 - 125.00 %. |
| ratio of the geometric means | 95.93 | 2-Sided | 90 | 90.83 | 101.33 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | PK similarity of the two treatments was to be concluded if the 90% CI for the ratio of adjusted geometric means was within 80.00 - 125.00 %. |
| ratio of the geometric means | 96.05 | 2-Sided | 90 | 89.27 | 103.36 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |
| ratio of the geometric means | 98.11 | 2-Sided | 90 | 91.42 | 105.27 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |
| ratio of the geometric means | 97.19 | 2-Sided | 90 | 91.39 | 103.35 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |
| ratio of the geometric means | 97.97 | 2-Sided | 90 | 92.58 | 103.68 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |
| ratio of the geometric means | 98.83 | 2-Sided | 90 | 93.27 | 104.72 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |
| ratio of the geometric means | 98.01 | 2-Sided | 90 | 93.15 | 103.11 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |
| ratio of the geometric means | 100.16 | 2-Sided | 90 | 94.37 | 106.29 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |
| ratio of the geometric means | 97.02 | 2-Sided | 90 | 92.07 | 102.24 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |
| ratio of the geometric means | 100.94 | 2-Sided | 90 | 94.24 | 108.12 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |
| ratio of the geometric means | 95.37 | 2-Sided | 90 | 89.53 | 101.60 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |
| ratio of the geometric means | 101.36 | 2-Sided | 90 | 92.51 | 111.05 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |
| ratio of the geometric means | 94.04 | 2-Sided | 90 | 86.01 | 102.82 | An analysis of covariance (ANCOVA) model on the logarithmic scale with fixed effects for treatment and trial site as well as age (as recorded at the time of informed consent) and body weight (as recorded at baseline) as continuous covariates. | Non-Inferiority or Equivalence | No formal testing; two-sided 90% CI for the ratio of adjusted geometric means was calculated. |