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Pharmacokinetics and Safety of BI 695501 Administered Via Prefilled Syringe or Autoinjector

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ClinicalTrials.gov Identifier: NCT02606903
Recruitment Status : Completed
First Posted : November 17, 2015
Results First Posted : December 27, 2018
Last Update Posted : December 27, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: BI 695501 prefilled syringe
Drug: BI 695501 autoinjector
Enrollment 71
Recruitment Details  
Pre-assignment Details This was randomized, single-dose, parallel-arm, open-label Phase I trial with healthy male subjects.
Arm/Group Title BI 695501 Autoinjector (AI) BI 695501 Pre-filled Syringe (PFS)
Hide Arm/Group Description Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product) Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
Period Title: Overall Study
Started 35 36
Completed 35 36
Not Completed 0 0
Arm/Group Title BI 695501 Autoinjector (AI) BI 695501 Pre-filled Syringe (PFS) Total
Hide Arm/Group Description Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product) Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product) Total of all reporting groups
Overall Number of Baseline Participants 35 36 71
Hide Baseline Analysis Population Description
All subjects randomized set (RND): The RND consisted of all subjects in the subjects enrolled set (all subjects who provided informed consent for this trial.) who were randomized to trial medication. For analyses and displays based on RND, subjects were classified according to randomized treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 35 participants 36 participants 71 participants
39.3  (13.77) 40.1  (13.32) 39.7  (13.45)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 36 participants 71 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
35
 100.0%
36
 100.0%
71
 100.0%
1.Primary Outcome
Title Maximum Measured Concentration of BI 695501 in Plasma (Cmax)
Hide Description Maximum measured concentration of BI 695501 in plasma (Cmax). The rate and extent of absorption of BI 695501 by assessment of maximum plasma concentration following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results.
Time Frame PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PKS): The PKS consisted of all randomized subjects who received the single dose of trial medication, had at least one evaluable primary pharmacokinetic parameter, and were without important protocol deviations or violations thought to significantly affect the pharmacokinetics of BI 695501.
Arm/Group Title BI 695501 Autoinjector (AI) BI 695501 Pre-filled Syringe (PFS)
Hide Arm/Group Description:
Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product)
Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
Overall Number of Participants Analyzed 35 36
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Micro-gram (µg) per milliliter (mL)
3.79
(27.4%)
3.48
(51.0%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BI 695501 Autoinjector (AI), BI 695501 Pre-filled Syringe (PFS)
Comments Analysis of variance (ANOVA) model on the log scale was used including treatment and body mass index (BMI) group as fixed effects
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means (%)
Estimated Value 110.19
Confidence Interval (2-Sided) 90%
96.80 to 125.44
Parameter Dispersion
Type: Standard Deviation
Value: 33.603
Estimation Comments Relative bioavailability was estimated by the ratio (AI/PFS) of the adjusted geometric means (gMean). Standard deviation is actually inter-individual geometric coefficient of variation (%).
2.Primary Outcome
Title Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 to 1032 Hours After Dose (AUC0-1032)
Hide Description Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 to 1032 hours after dose (AUC0-1032). The rate and extent of absorption of BI 695501 by assessment of AUC0-1032 following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results.
Time Frame PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PKS): The PKS consisted of all randomized subjects who received the single dose of trial medication, had at least one evaluable primary pharmacokinetic parameter, and were without important protocol deviations or violations thought to significantly affect the pharmacokinetics of BI 695501.
Arm/Group Title BI 695501 Autoinjector (AI) BI 695501 Pre-filled Syringe (PFS)
Hide Arm/Group Description:
Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product)
Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
Overall Number of Participants Analyzed 35 35
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg*h/mL
1810
(47.5%)
1840
(47.1%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BI 695501 Autoinjector (AI), BI 695501 Pre-filled Syringe (PFS)
Comments Analysis of variance (ANOVA) model on the log scale was used including treatment and BMI group as fixed effects
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means (%)
Estimated Value 100.14
Confidence Interval (2-Sided) 90%
85.15 to 117.76
Parameter Dispersion
Type: Standard Deviation
Value: 42.354
Estimation Comments Relative bioavailability was estimated by the ratio (AI/PFS) of the adjusted geometric means (gMean). Standard deviation is actually inter-individual geometric coefficient of variation (%).
3.Primary Outcome
Title Area Under the Concentration-time Curve of the BI 695501 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity)
Hide Description Area under the concentration-time curve of the BI 695501 in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) based on observed concentration at time of last measurable concentration. The rate and extent of absorption of BI 695501 by assessment of (AUC0-∞) following administration via AI or via PFS of a single dose of 40 mg BI 695501. During analysis, it was realized that the PK sample on Day 43 had originally been mistakenly associated with a 1032 h time point, rather than with 1008 h. However, PK parameters are calculated using actual values so this did not impact the analysis results.
Time Frame PK plasma samples were taken at: 1 hour (h) before drug administration and 1h, 4h, 8h,12h, 24h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 144h, 168h, 216h, 336h, 504h, 672h, 840h, 1008h after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set (PKS): The PKS consisted of all randomized subjects who received the single dose of trial medication, had at least one evaluable primary pharmacokinetic parameter, and were without important protocol deviations or violations thought to significantly affect the pharmacokinetics of BI 695501.
Arm/Group Title BI 695501 Autoinjector (AI) BI 695501 Pre-filled Syringe (PFS)
Hide Arm/Group Description:
Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product)
Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
Overall Number of Participants Analyzed 35 35
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg*h/mL
2080
(58.2%)
2110
(58.0%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BI 695501 Autoinjector (AI), BI 695501 Pre-filled Syringe (PFS)
Comments Analysis of variance (ANOVA) model on the log scale was used including treatment and BMI group as fixed effects
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means (%)
Estimated Value 100.22
Confidence Interval (2-Sided) 90%
82.13 to 122.29
Parameter Dispersion
Type: Standard Deviation
Value: 53.137
Estimation Comments Relative bioavailability was estimated by the ratio (AI/PFS) of the adjusted geometric means (gMean). Standard deviation is actually inter-individual geometric coefficient of variation (%).
4.Secondary Outcome
Title Number of Subjects With Drug-related Adverse Events (AEs)
Hide Description Number of subjects with drug-related Adverse Events (AEs). Any event with an onset after the administration of the trial medication up to a period of 70 days 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.
Time Frame From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set (SAF): The SAF consisted of all subjects in the enrolled set who received at least one dose of trial medication and subjects were classified according to treatment received.
Arm/Group Title BI 695501 Autoinjector (AI) BI 695501 Pre-filled Syringe (PFS)
Hide Arm/Group Description:
Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product)
Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
Overall Number of Participants Analyzed 35 36
Measure Type: Number
Unit of Measure: Number of Subjects
20 16
Time Frame From the first drug administration until 43 days observation period after drug administration and up to 70 days safety follow up period
Adverse Event Reporting Description Regular investigator assessment at study visits. The safety analysis set was used which consisted of all subjects who provided informed consent and who received at least one dose of trial medication.
 
Arm/Group Title BI 695501 Autoinjector (AI) BI 695501 Pre-filled Syringe (PFS)
Hide Arm/Group Description Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in auto injector via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Test Product) Subject received single dose of 40 milligram (mg)/ 0.8 milliliters (mL) BI 695501 solution for injection in pre-filled syringe via subcutaneous injection followed by a 43-day observation period and up to 70 days safety follow-up period. (Reference Product)
All-Cause Mortality
BI 695501 Autoinjector (AI) BI 695501 Pre-filled Syringe (PFS)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
BI 695501 Autoinjector (AI) BI 695501 Pre-filled Syringe (PFS)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/35 (0.00%)   0/36 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BI 695501 Autoinjector (AI) BI 695501 Pre-filled Syringe (PFS)
Affected / at Risk (%) Affected / at Risk (%)
Total   28/35 (80.00%)   23/36 (63.89%) 
General disorders     
Fatigue  1  1/35 (2.86%)  2/36 (5.56%) 
Influenza like illness  1  0/35 (0.00%)  2/36 (5.56%) 
Injection site erythema  1  18/35 (51.43%)  13/36 (36.11%) 
Injection site induration  1  4/35 (11.43%)  1/36 (2.78%) 
Injection site pain  1  3/35 (8.57%)  0/36 (0.00%) 
Injection site pruritus  1  1/35 (2.86%)  2/36 (5.56%) 
Injection site swelling  1  7/35 (20.00%)  3/36 (8.33%) 
Infections and infestations     
Nasopharyngitis  1  8/35 (22.86%)  2/36 (5.56%) 
Injury, poisoning and procedural complications     
Contusion  1  3/35 (8.57%)  0/36 (0.00%) 
Musculoskeletal and connective tissue disorders     
Neck pain  1  2/35 (5.71%)  1/36 (2.78%) 
Pain in extremity  1  2/35 (5.71%)  0/36 (0.00%) 
Back pain  1  3/35 (8.57%)  1/36 (2.78%) 
Nervous system disorders     
Headache  1  4/35 (11.43%)  6/36 (16.67%) 
Paraesthesia  1  2/35 (5.71%)  1/36 (2.78%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain  1  2/35 (5.71%)  0/36 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02606903    
Other Study ID Numbers: 1297.6
2015-003029-32 ( EudraCT Number )
First Submitted: November 16, 2015
First Posted: November 17, 2015
Results First Submitted: September 11, 2017
Results First Posted: December 27, 2018
Last Update Posted: December 27, 2018