Healthy Volunteers
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to evaluate the bioavailability of teduglutide administered as a single subcutaneous (SC) fixed dose (depending upon participant weightband assignment) delivered by a syringe injection and the same fixed dose delivered by the pen injector in healthy participants.
Detailed description
This is a 2-period crossover study and consists of two cohorts. Cohort 1 consists of participant's with greater than or equal to (\>=) 40.0 kilogram (kg) to lesser than or equal to (\<=) 75.0 kg of weight and Cohort 2 consists of participant's with greater than (\>) 75.0 kg to \<= 120.0 kg of weight. Participants in each cohort will be randomized to 1 of 2 treatment sequences AB or BA. Randomization will be stratified by injection site (i.e., thigh, abdomen, and arm) within each cohort.
Interventions
DRUGTeduglutide
Participants received 3 mg or 4 mg of Teduglutide SC syringe injection followed by pen injector or vice versa depending upon the treatment sequence AB or BA on Day 1 of Treatment Periods 1 and 2.
DEVICESyringe Injection
Teduglutide was administered using syringe.
DEVICEPen injector
Teduglutide was administered using pen injector.
Sponsors
Takeda Development Center Americas, Inc.
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* An understanding, ability, and willingness to fully comply with study procedures and restrictions. * Ability to voluntarily provide written, signed, and dated informed consent and assent as applicable to participate in the study. * Aged 18 - 45 inclusive at the time of consent. The date of signature of the informed consent is defined as the beginning of the screening period. This inclusion criterion will only be assessed at the first screening visit. * Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential. * Considered healthy by the investigator. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a full physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, coagulation (as appropriate), serum chemistry, and urinalysis. * Body mass index (BMI) \>= 18.0 and l\<=32.0 kilogram per square meter (kg/m\^2) at screening. Body weight for a participant in Cohort 1 will be \>= 40.0 kg to \<= 75.0 kg, and body weight for a participant in Cohort 2 will be \> 75.0 kg to \<= 120.0 kg, inclusive. This inclusion criterion will be assessed at the screening visit and confirmed at first check-in.
Exclusion criteria
* History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments. * Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the participant unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures. * Positive PCR (polymerase chain reaction) test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), either with the absence or presence of the clinical symptoms of Coronavirus disease 2019 (COVID-19). * Known or suspected intolerance or hypersensitivity to teduglutide, closely-related compounds, or any of the stated ingredients. * Significant illness, as judged by the investigator, within 2 weeks of the first dose of teduglutide. * Known history of alcohol or other substance abuse within the last year prior to screening. * Donation of blood or blood products (e.g. plasma or platelets) within 60 days prior to receiving the first dose of teduglutide. * Pregnant or lactating female. * Within 30 days prior to the first dose of teduglutide: 1. Have used an investigational product (if elimination half-life is lesser than \[\<\] 6 days, otherwise 5 half-lives) 2. Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's (or designee's) opinion, may impact this study 3. Have had any substantial changes in eating habits, as assessed by the investigator (or designee) * Use of dipeptidyl peptidase 4 inhibitors within 30 days or 5 half-lives, whichever is greater, prior to administration of the first dose of teduglutide. * Confirmed systolic blood pressure \> 140 millimeter of mercury (mmHg) or \< 90 mmHg, and diastolic blood pressure \> 90 mmHg or \< 40 mmHg at screening. * Twelve-lead electrocardiogram (ECG) demonstrating QTcF \> 450 milliseconds (msec) at screening. If the QTcF exceeds the aforementioned limits, the ECG should be repeated 2 more times and the average of the 3 QTcF values should be used to determine the participants eligibility. * Positive screen for drugs of abuse or alcohol at screening and at each check-in. * Male participants who consume more than 21 units of alcohol per week or regularly consume more than 3 units per day. Female participants who consume more than 14 units of alcohol per week or regularly consume more than 2 units per day. (1 alcohol unit=150 milliliter \[mL\] of wine, or 360 mL of beer, or 45 mL of 45 percent \[%\] alcohol). * Positive Human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody screen at screening. * Use of tobacco in any form (e.g. smoking or chewing) or other nicotine-containing products in any form (e.g. gum, patch) based on participant self-reporting. Ex-users must report that they have stopped using tobacco for at least 3 months prior to receiving the first dose of teduglutide. * Routine consumption of more than 2 units of caffeine per day or participants who experience caffeine withdrawal headaches. One caffeine unit is contained in the following items: one 6 ounce (oz) (180 mL) cup of coffee, two 12 oz (360 mL) cans of cola, one 12 oz (360 mL) cup of tea, three 1 oz (85 gram \[g\]) chocolate bars. * Prior screen failure, randomization, participation, or enrollment in this study, or prior exposure to any Glucagon-like peptide 2 (GLP-2) analogs. * Presence of lesions, rashes, tattoos, and moles etc. on administration sites not allowing adequate conduct of injection site reaction and injection site injury assessment * Current use of any medication (including over-the-counter, herbal, or homeopathic preparations; with the exception of occasional use of ibuprofen \[1.2 g per 24 hour period\] or acetaminophen \[2 g per 24 hour period\]). Current use is defined as use within 14 days of the first dose of teduglutide and throughout the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2 | — |
| Maximum Observed Plasma Concentration (Cmax) of Teduglutide | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2 | Cmax is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. |
| Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) [Tmax] of Teduglutide | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2 | — |
| Terminal Disposition Phase Rate Constant (Lambda z) of Teduglutide | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2 | — |
| Terminal Disposition Phase Half-Life (t1/2z) of Teduglutide | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2 | — |
| Apparent Total Body Clearance (CL/F) of Teduglutide | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2 | CL/F for extravascular administration divided by the fraction of dose absorbed of teduglutide was assessed and reported. |
| Apparent Volume of Distribution (Vz/F) of Teduglutide | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2 | Vz/F associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed of teduglutide was assessed and reported. |
| Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2 | AUC0-last of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported. |
| Number of Participants With Clinically Significant Change in Vital Signs | From the start of study drug administration up to follow-up (up to 42 days) | Vital signs included body temperature, respiratory rate, blood pressure, and heart rate. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | From the start of study drug administration up to follow-up (up to 42 days) | Clinical laboratory assessments included hematology, serum chemistry, coagulation, and urinalysis. Changes in laboratory values may be considered as AE if they were judged to be clinically significant. |
| Number of Participants With Clinically Significant Changes in Physical Examinations | From the start of study drug administration up to follow-up (up to 42 days) | Physical examination included examination of respiratory, cardiovascular, and gastrointestinal system. |
| Number of Participants With Device Malfunction | Day 1 | Number of participants with device malfunction was assessed and reported. The site staff reported any malfunctions whilst using the device. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From the start of study drug administration up to follow-up (up to 42 days) | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an AE that started or worsened at the time of or after study drug administration. Number of participants with TEAEs included injection site reactions and injection site injury assessments. |
| Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2 | Cmax of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported. |
| Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2 | AUC0-infinity of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 13 January 2021 to 20 August 2021.
Pre-assignment details
Healthy participants were enrolled in 1 of the 2 cohorts of this 2-period cross-over study to receive teduglutide (TAK-633) 3 or 4 milligrams (mg), subcutaneously by syringe injection (Treatment A1 for Cohort 1 and Treatment A2 for Cohort 2) or through pen injector (Treatment B1 for Cohort 1 and Treatment B2 for Cohort 2). Randomization was stratified by injection site (thigh, abdomen, and arm) within each cohort .
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1, Then Treatment B1 (A1B1) Teduglutide, 3 mg, subcutaneous (SC) injection using a syringe, once on Day 1 of Treatment Period 1 (Treatment A1), followed by same dose SC pen injector, once on Day 1 of Treatment Period 2 (Treatment B1). A Washout Period of 7 days was maintained between Treatment Periods 1 and 2. Participants with \>=40.0 kg to \<=75.0 kg of weight were included in Cohort 1 | 16 |
| Cohort 1 (Teduglutide 3 mg): Treatment B1, Then Treatment A1 (B1A1) Teduglutide, 3 mg, SC pen injector, once on Day 1 of Treatment Period 1 (Treatment B1), followed by same dose SC injection using a syringe, once on Day 1 of Treatment Period 2 (Treatment A1). A Washout Period of 7 days was maintained between the Treatment Periods 1 and 2. Participants with \>=40.0 kg to \<=75.0 kg of weight were included in Cohort 1. | 16 |
| Cohort 2 (Teduglutide 4 mg): Treatment A2, Then Treatment B2 (A2B2) Teduglutide, 4 mg, SC injection using a syringe, once on Day 1 of Treatment Period 1 (Treatment A2), followed by same dose SC pen injector, once on Day 1 of Treatment Period 2 (Treatment B2). A Washout Period of 7 days was maintained between Treatment Periods 1 and 2. Participants \>75.0 kg to \<=120.0 kg of weight were included in Cohort 2. | 16 |
| Cohort 2 (Teduglutide 4 mg): Treatment B2, Then Treatment A2 (B2A2) Teduglutide, 4 mg, SC pen injector, once on Day 1 of Treatment Period 1 (Treatment B2), followed by same dose SC injection using a syringe, once on Day 1 of Treatment Period 2 (Treatment A2). A Washout Period of 7 days was maintained between Treatment Periods 1 and 2. Participants \>75.0 kg to \<=120.0 kg of weight were included in Cohort 2. | 16 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 2 (Day 1) | Lost to Follow-up | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 (Teduglutide 3 mg): Treatment A1, Then Treatment B1 (A1B1) | Total | Cohort 2 (Teduglutide 4 mg): Treatment B2, Then Treatment A2 (B2A2) | Cohort 2 (Teduglutide 4 mg): Treatment A2, Then Treatment B2 (A2B2) | Cohort 1 (Teduglutide 3 mg): Treatment B1, Then Treatment A1 (B1A1) |
|---|---|---|---|---|---|
| Age, Continuous | 31.8 years | 33.2 years | 35.9 years | 32.5 years | 32.4 years |
| Body Mass Index (BMI) | 24.271 kg/m^2 | 26.313 kg/m^2 | 27.530 kg/m^2 | 28.558 kg/m^2 | 24.891 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 42 Participants | 9 Participants | 9 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 22 Participants | 7 Participants | 7 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 163.19 cm | 169.11 cm | 175.38 cm | 173.81 cm | 164.06 cm |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 11 Participants | 3 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 49 Participants | 13 Participants | 10 Participants | 14 Participants |
| Region of Enrollment United States | 16 Participants | 64 Participants | 16 Participants | 16 Participants | 16 Participants |
| Sex: Female, Male Female | 9 Participants | 21 Participants | 1 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 7 Participants | 43 Participants | 15 Participants | 14 Participants | 7 Participants |
| Weight | 64.38 kg | 75.49 kg | 84.68 kg | 86.39 kg | 66.51 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 13 / 32 | 10 / 32 | 9 / 32 | 1 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 |
Outcome results
Primary
Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Population: Pharmacokinetic (PK) Set included all participants who received at least one dose of the study drug and have at least 1 quantifiable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide | 217.2 ng*hour/mL | Geometric Coefficient of Variation 21 |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide | 237.2 ng*hour/mL | Geometric Coefficient of Variation 22.1 |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide | 221.9 ng*hour/mL | Geometric Coefficient of Variation 21.2 |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide | 253.0 ng*hour/mL | Geometric Coefficient of Variation 21.4 |
90% CI: [104.83, 113.8]
90% CI: [108.32, 119.95]
Primary
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Population: PK Set included all participants who received at least one dose of the study drug and have at least 1 quantifiable plasma concentration. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide | 227.6 ng*hr/mL | Geometric Coefficient of Variation 21.1 |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide | 249.2 ng*hr/mL | Geometric Coefficient of Variation 20.8 |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide | 227.1 ng*hr/mL | Geometric Coefficient of Variation 20.8 |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide | 268.2 ng*hr/mL | Geometric Coefficient of Variation 22.2 |
90% CI: [105.51, 113.51]
90% CI: [112.31, 124.83]
Primary
Maximum Observed Plasma Concentration (Cmax) of Teduglutide
Cmax is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Population: PK Set included all participants who received at least one dose of the study drug and have at least 1 quantifiable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Maximum Observed Plasma Concentration (Cmax) of Teduglutide | 33.90 ng/mL | Geometric Coefficient of Variation 37.7 |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Maximum Observed Plasma Concentration (Cmax) of Teduglutide | 33.31 ng/mL | Geometric Coefficient of Variation 37.6 |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Maximum Observed Plasma Concentration (Cmax) of Teduglutide | 31.99 ng/mL | Geometric Coefficient of Variation 34.8 |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Maximum Observed Plasma Concentration (Cmax) of Teduglutide | 29.58 ng/mL | Geometric Coefficient of Variation 32.6 |
90% CI: [88.5, 109.11]
90% CI: [83.8, 102.05]
Secondary
Apparent Total Body Clearance (CL/F) of Teduglutide
CL/F for extravascular administration divided by the fraction of dose absorbed of teduglutide was assessed and reported.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Population: PK Set included all participants who received at least one dose of the study drug and have at least 1 quantifiable plasma concentration. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Apparent Total Body Clearance (CL/F) of Teduglutide | 13.48 Liter(L)/hr | Standard Deviation 3.206 |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Apparent Total Body Clearance (CL/F) of Teduglutide | 12.31 Liter(L)/hr | Standard Deviation 2.9332 |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Apparent Total Body Clearance (CL/F) of Teduglutide | 17.97 Liter(L)/hr | Standard Deviation 3.5737 |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Apparent Total Body Clearance (CL/F) of Teduglutide | 15.27 Liter(L)/hr | Standard Deviation 3.5042 |
Secondary
Apparent Volume of Distribution (Vz/F) of Teduglutide
Vz/F associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed of teduglutide was assessed and reported.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Population: PK Set included all participants who received at least one dose of the study drug and have at least 1 quantifiable plasma concentration. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Apparent Volume of Distribution (Vz/F) of Teduglutide | 36.85 L | Standard Deviation 18.837 |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Apparent Volume of Distribution (Vz/F) of Teduglutide | 31.86 L | Standard Deviation 15.382 |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Apparent Volume of Distribution (Vz/F) of Teduglutide | 49.84 L | Standard Deviation 27.394 |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Apparent Volume of Distribution (Vz/F) of Teduglutide | 51.01 L | Standard Deviation 23.867 |
Secondary
Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site
AUC0-last of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Population: PK Set included all participants who received at least one dose of the study drug and have at least 1 quantifiable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 241.2 ng*hr/mL | Geometric Coefficient of Variation 14 |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 205.8 ng*hr/mL | Geometric Coefficient of Variation 29.1 |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 202.2 ng*hr/mL | Geometric Coefficient of Variation 14.4 |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 277.6 ng*hr/mL | Geometric Coefficient of Variation 9.1 |
| Cohort 1 (Teduglutide 3 mg): Pen Injector in Arm | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 216.6 ng*hr/mL | Geometric Coefficient of Variation 27.8 |
| Cohort 1 (Teduglutide 3 mg): Pen Injector in Thigh | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 215.2 ng*hr/mL | Geometric Coefficient of Variation 16.7 |
| Cohort 2 (Teduglutide 4 mg): Syringe Injection in Abdomen | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 219.6 ng*hr/mL | Geometric Coefficient of Variation 17.2 |
| Cohort 2 (Teduglutide 4 mg): Syringe Injection in Arm | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 222.6 ng*hr/mL | Geometric Coefficient of Variation 27.9 |
| Cohort 2 (Teduglutide 4 mg): Syringe Injection in Thigh | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 224.1 ng*hr/mL | Geometric Coefficient of Variation 20.3 |
| Cohort 2 (Teduglutide 4 mg): Pen Injector in Abdomen | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 239.5 ng*hr/mL | Geometric Coefficient of Variation 19 |
| Cohort 2 (Teduglutide 4 mg): Pen Injector in Arm | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 277.3 ng*hr/mL | Geometric Coefficient of Variation 23.3 |
| Cohort 2 (Teduglutide 4 mg): Pen Injector in Thigh | Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide by Injection Site | 246.4 ng*hr/mL | Geometric Coefficient of Variation 21.3 |
Secondary
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site
AUC0-infinity of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Population: PK Set included all participants who received at least one dose of the study drug and have at least 1 quantifiable plasma concentration. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 246.6 ng*hr/mL | Geometric Coefficient of Variation 13.2 |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 213.0 ng*hr/mL | Geometric Coefficient of Variation 29.5 |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 218.6 ng*hr/mL | Geometric Coefficient of Variation 18.7 |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 282.3 ng*hr/mL | Geometric Coefficient of Variation 9.1 |
| Cohort 1 (Teduglutide 3 mg): Pen Injector in Arm | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 229.6 ng*hr/mL | Geometric Coefficient of Variation 26.8 |
| Cohort 1 (Teduglutide 3 mg): Pen Injector in Thigh | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 229.2 ng*hr/mL | Geometric Coefficient of Variation 18.6 |
| Cohort 2 (Teduglutide 4 mg): Syringe Injection in Abdomen | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 224.7 ng*hr/mL | Geometric Coefficient of Variation 17.6 |
| Cohort 2 (Teduglutide 4 mg): Syringe Injection in Arm | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 228.2 ng*hr/mL | Geometric Coefficient of Variation 27.1 |
| Cohort 2 (Teduglutide 4 mg): Syringe Injection in Thigh | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 228.7 ng*hr/mL | Geometric Coefficient of Variation 20 |
| Cohort 2 (Teduglutide 4 mg): Pen Injector in Abdomen | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 247.0 ng*hr/mL | Geometric Coefficient of Variation 19.7 |
| Cohort 2 (Teduglutide 4 mg): Pen Injector in Arm | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 296.8 ng*hr/mL | Geometric Coefficient of Variation 24.4 |
| Cohort 2 (Teduglutide 4 mg): Pen Injector in Thigh | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site | 268.1 ng*hr/mL | Geometric Coefficient of Variation 20.9 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site
Cmax of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Population: PK Set included all participants who received at least one dose of the study drug and have at least 1 quantifiable plasma concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 40.84 ng/mL | Geometric Coefficient of Variation 29.7 |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 31.66 ng/mL | Geometric Coefficient of Variation 41.6 |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 29.02 ng/mL | Geometric Coefficient of Variation 35.2 |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 43.65 ng/mL | Geometric Coefficient of Variation 20.7 |
| Cohort 1 (Teduglutide 3 mg): Pen Injector in Arm | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 28.73 ng/mL | Geometric Coefficient of Variation 43.9 |
| Cohort 1 (Teduglutide 3 mg): Pen Injector in Thigh | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 27.91 ng/mL | Geometric Coefficient of Variation 27.3 |
| Cohort 2 (Teduglutide 4 mg): Syringe Injection in Abdomen | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 26.86 ng/mL | Geometric Coefficient of Variation 25.9 |
| Cohort 2 (Teduglutide 4 mg): Syringe Injection in Arm | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 38.28 ng/mL | Geometric Coefficient of Variation 43.8 |
| Cohort 2 (Teduglutide 4 mg): Syringe Injection in Thigh | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 32.97 ng/mL | Geometric Coefficient of Variation 25 |
| Cohort 2 (Teduglutide 4 mg): Pen Injector in Abdomen | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 28.14 ng/mL | Geometric Coefficient of Variation 30.4 |
| Cohort 2 (Teduglutide 4 mg): Pen Injector in Arm | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 32.33 ng/mL | Geometric Coefficient of Variation 33.8 |
| Cohort 2 (Teduglutide 4 mg): Pen Injector in Thigh | Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site | 28.73 ng/mL | Geometric Coefficient of Variation 35.5 |
Secondary
Number of Participants With Clinically Significant Change in Vital Signs
Vital signs included body temperature, respiratory rate, blood pressure, and heart rate.
Time frame: From the start of study drug administration up to follow-up (up to 42 days)
Population: Safety Set included all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Number of Participants With Clinically Significant Change in Vital Signs | 0 Participants |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Number of Participants With Clinically Significant Change in Vital Signs | 0 Participants |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Number of Participants With Clinically Significant Change in Vital Signs | 0 Participants |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Number of Participants With Clinically Significant Change in Vital Signs | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
Clinical laboratory assessments included hematology, serum chemistry, coagulation, and urinalysis. Changes in laboratory values may be considered as AE if they were judged to be clinically significant.
Time frame: From the start of study drug administration up to follow-up (up to 42 days)
Population: Safety Set included all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | 0 Participants |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | 0 Participants |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | 0 Participants |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Physical Examinations
Physical examination included examination of respiratory, cardiovascular, and gastrointestinal system.
Time frame: From the start of study drug administration up to follow-up (up to 42 days)
Population: Safety Set included all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Number of Participants With Clinically Significant Changes in Physical Examinations | 0 Participants |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Number of Participants With Clinically Significant Changes in Physical Examinations | 0 Participants |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Number of Participants With Clinically Significant Changes in Physical Examinations | 0 Participants |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Number of Participants With Clinically Significant Changes in Physical Examinations | 0 Participants |
Secondary
Number of Participants With Device Malfunction
Number of participants with device malfunction was assessed and reported. The site staff reported any malfunctions whilst using the device.
Time frame: Day 1
Population: Safety Set included all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Number of Participants With Device Malfunction | 0 Participants |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Number of Participants With Device Malfunction | 0 Participants |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Number of Participants With Device Malfunction | 0 Participants |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Number of Participants With Device Malfunction | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an AE that started or worsened at the time of or after study drug administration. Number of participants with TEAEs included injection site reactions and injection site injury assessments.
Time frame: From the start of study drug administration up to follow-up (up to 42 days)
Population: Safety Set included all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 13 Participants |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 10 Participants |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 9 Participants |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 5 Participants |
Secondary
Terminal Disposition Phase Half-Life (t1/2z) of Teduglutide
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Population: PK Set included all participants who received at least one dose of the study drug and have at least 1 quantifiable plasma concentration. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Terminal Disposition Phase Half-Life (t1/2z) of Teduglutide | 1.930 hour | Standard Deviation 1.107 |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Terminal Disposition Phase Half-Life (t1/2z) of Teduglutide | 1.797 hour | Standard Deviation 0.8341 |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Terminal Disposition Phase Half-Life (t1/2z) of Teduglutide | 1.903 hour | Standard Deviation 0.9107 |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Terminal Disposition Phase Half-Life (t1/2z) of Teduglutide | 2.385 hour | Standard Deviation 1.2292 |
Secondary
Terminal Disposition Phase Rate Constant (Lambda z) of Teduglutide
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Population: PK Set included all participants who received at least one dose of the study drug and have at least 1 quantifiable plasma concentration. Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Terminal Disposition Phase Rate Constant (Lambda z) of Teduglutide | 0.4055 1/hr | Geometric Coefficient of Variation 51.2 |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Terminal Disposition Phase Rate Constant (Lambda z) of Teduglutide | 0.4191 1/hr | Geometric Coefficient of Variation 41 |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Terminal Disposition Phase Rate Constant (Lambda z) of Teduglutide | 0.3971 1/hr | Geometric Coefficient of Variation 41.8 |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Terminal Disposition Phase Rate Constant (Lambda z) of Teduglutide | 0.3236 1/hr | Geometric Coefficient of Variation 48.1 |
Secondary
Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) [Tmax] of Teduglutide
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 24 hours post-dose of Treatment Period 1 and Treatment Period 2
Population: PK Set included all participants who received at least one dose of the study drug and have at least 1 quantifiable plasma concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection) | Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) [Tmax] of Teduglutide | 4.002 hour |
| Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector) | Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) [Tmax] of Teduglutide | 4.001 hour |
| Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection) | Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) [Tmax] of Teduglutide | 4.999 hour |
| Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector) | Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) [Tmax] of Teduglutide | 4.507 hour |