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Trial · Interventional

CompletedPhase 1Results postedRegistry data

A Study to Evaluate the Bioavailability of Teduglutide Administered Subcutaneously by Syringe Injection Versus Pen Injector in Healthy Adult Participants

Overview

Status
Completed
Phase
Phase 1
Enrollment
64 participants (actual)
Sponsor
Shire · Industry
Design
Randomized · Open label (no masking)
Countries
1 country

United States

Start
13 Jan 2021
Primary completion
20 Aug 2021
Completion
20 Aug 2021
First posted
10 Jul 2020
Last update posted
4 Oct 2022
Conditions
Healthy Volunteers

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20212022
  1. Ph 1

    A Study to Evaluate the Bioavailability of Teduglutide Administered Subcutaneously by Syringe Injection Versus Pen Injector in Healthy Adult Participants

    NCT04465396

    13 Jan 2021 to 20 Aug 2021

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • TeduglutideDrug
  • Syringe InjectionDevice
  • Pen injectorDevice

Arms4

  • Experimental

    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.

  • Experimental

    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.

  • Experimental

    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.

  • Experimental

    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.

Primary outcomes3

Outcomes the sponsor listed as primary.

  1. 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

  2. Maximum Observed Plasma Concentration (Cmax) 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

    Registry description

    Cmax is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

  3. 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

Secondary outcomes(13)
  1. 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

    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

    Registry description

    AUC0-last of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported.

  2. Maximum Observed Plasma Concentration (Cmax) of Teduglutide by Injection Site

    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

    Registry description

    Cmax of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported.

  3. Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site

    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

    Registry description

    AUC0-infinity of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported.

  4. 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

  5. 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

  6. 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

  7. Apparent Total Body Clearance (CL/F) 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

    Registry description

    CL/F for extravascular administration divided by the fraction of dose absorbed of teduglutide was assessed and reported.

  8. Apparent Volume of Distribution (Vz/F) 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

    Registry description

    Vz/F associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed of teduglutide was assessed and reported.

  9. Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    Time frame · From the start of study drug administration up to follow-up (up to 42 days)

    Registry description

    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.

  10. Number of Participants With Clinically Significant Change in Vital Signs

    Time frame · From the start of study drug administration up to follow-up (up to 42 days)

    Registry description

    Vital signs included body temperature, respiratory rate, blood pressure, and heart rate.

  11. Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments

    Time frame · From the start of study drug administration up to follow-up (up to 42 days)

    Registry description

    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.

  12. Number of Participants With Clinically Significant Changes in Physical Examinations

    Time frame · From the start of study drug administration up to follow-up (up to 42 days)

    Registry description

    Physical examination included examination of respiratory, cardiovascular, and gastrointestinal system.

  13. Number of Participants With Device Malfunction

    Time frame · Day 1

    Registry description

    Number of participants with device malfunction was assessed and reported. The site staff reported any malfunctions whilst using the device.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeGeometric mean· 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

Area Under the Plasma Concentration Verse Time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) of Teduglutide

GroupValue (ng*hour/mL)Spread
Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection)217.221.0
Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector)237.222.1
Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection)221.921.2
Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector)253.021.4
Primary outcomeGeometric mean· 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

GroupValue (ng/mL)Spread
Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection)33.9037.7
Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector)33.3137.6
Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection)31.9934.8
Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector)29.5832.6
Primary outcomeGeometric mean· 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

Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide

GroupValue (ng*hr/mL)Spread
Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection)227.621.1
Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector)249.220.8
Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection)227.120.8
Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector)268.222.2
Secondary and other outcome results(5)
Secondary outcomeGeometric mean· 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

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

GroupValue (ng*hr/mL)Spread
Cohort 1 (Teduglutide 3 mg): Syringe Injection in Abdomen241.214.0
Cohort 1 (Teduglutide 3 mg): Syringe Injection in Arm205.829.1
Cohort 1 (Teduglutide 3 mg): Syringe Injection in Thigh202.214.4
Cohort 1 (Teduglutide 3 mg): Pen Injector in Abdomen277.69.1
Cohort 1 (Teduglutide 3 mg): Pen Injector in Arm216.627.8
Cohort 1 (Teduglutide 3 mg): Pen Injector in Thigh215.216.7
Cohort 2 (Teduglutide 4 mg): Syringe Injection in Abdomen219.617.2
Cohort 2 (Teduglutide 4 mg): Syringe Injection in Arm222.627.9
Cohort 2 (Teduglutide 4 mg): Syringe Injection in Thigh224.120.3
Cohort 2 (Teduglutide 4 mg): Pen Injector in Abdomen239.519.0
Cohort 2 (Teduglutide 4 mg): Pen Injector in Arm277.323.3
Cohort 2 (Teduglutide 4 mg): Pen Injector in Thigh246.421.3
Secondary outcomeGeometric mean· 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 by Injection Site

GroupValue (ng/mL)Spread
Cohort 1 (Teduglutide 3 mg): Syringe Injection in Abdomen40.8429.7
Cohort 1 (Teduglutide 3 mg): Syringe Injection in Arm31.6641.6
Cohort 1 (Teduglutide 3 mg): Syringe Injection in Thigh29.0235.2
Cohort 1 (Teduglutide 3 mg): Pen Injector in Abdomen43.6520.7
Cohort 1 (Teduglutide 3 mg): Pen Injector in Arm28.7343.9
Cohort 1 (Teduglutide 3 mg): Pen Injector in Thigh27.9127.3
Cohort 2 (Teduglutide 4 mg): Syringe Injection in Abdomen26.8625.9
Cohort 2 (Teduglutide 4 mg): Syringe Injection in Arm38.2843.8
Cohort 2 (Teduglutide 4 mg): Syringe Injection in Thigh32.9725.0
Cohort 2 (Teduglutide 4 mg): Pen Injector in Abdomen28.1430.4
Cohort 2 (Teduglutide 4 mg): Pen Injector in Arm32.3333.8
Cohort 2 (Teduglutide 4 mg): Pen Injector in Thigh28.7335.5
Secondary outcomeGeometric mean· 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

Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-infinity) of Teduglutide by Injection Site

GroupValue (ng*hr/mL)Spread
Cohort 1 (Teduglutide 3 mg): Syringe Injection in Abdomen246.613.2
Cohort 1 (Teduglutide 3 mg): Syringe Injection in Arm213.029.5
Cohort 1 (Teduglutide 3 mg): Syringe Injection in Thigh218.618.7
Cohort 1 (Teduglutide 3 mg): Pen Injector in Abdomen282.39.1
Cohort 1 (Teduglutide 3 mg): Pen Injector in Arm229.626.8
Cohort 1 (Teduglutide 3 mg): Pen Injector in Thigh229.218.6
Cohort 2 (Teduglutide 4 mg): Syringe Injection in Abdomen224.717.6
Cohort 2 (Teduglutide 4 mg): Syringe Injection in Arm228.227.1
Cohort 2 (Teduglutide 4 mg): Syringe Injection in Thigh228.720.0
Cohort 2 (Teduglutide 4 mg): Pen Injector in Abdomen247.019.7
Cohort 2 (Teduglutide 4 mg): Pen Injector in Arm296.824.4
Cohort 2 (Teduglutide 4 mg): Pen Injector in Thigh268.120.9
Secondary outcomeMedian· 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

Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) [Tmax] of Teduglutide

GroupValue (hour)
Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection)4.002
Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector)4.001
Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection)4.999
Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector)4.507
Secondary outcomeGeometric mean· 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

GroupValue (1/hr)Spread
Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection)0.405551.2
Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector)0.419141.0
Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection)0.397141.8
Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector)0.323648.1

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Cohort 1 (Teduglutide 3 mg): Treatment A1 (Syringe Injection)Teduglutide, 3 mg, SC injection using a syringe, once on Day 1 of Treatment Period 1 and 2 (Treatment A1). Participants with \>=40.0 kg to \<=75.0 kg of weight were included in Cohort 1.0 / 320 / 3213 / 32
Cohort 1 (Teduglutide 3 mg): Treatment B1 (Pen Injector)Teduglutide, 3 mg, SC pen injector, once on Day 1 of Treatment Period 1 and 2 (Treatment B1). Participants with \>=40.0 kg to \<=75.0 kg of weight were included in Cohort 1.0 / 320 / 3210 / 32
Cohort 2 (Teduglutide 4 mg): Treatment A2 (Syringe Injection)Teduglutide, 4 mg, SC injection using a syringe, once on Day 1 of Treatment Period 1 and 2 (Treatment A2). Participants \>75.0 kg to \<=120.0 kg of weight were included in Cohort 2.0 / 320 / 329 / 32
Cohort 2 (Teduglutide 4 mg): Treatment B2 (Pen Injector)Teduglutide, 4 mg, SC pen injector, once on Day 1 of Treatment Period 1 and 2 (Treatment B2). Participants \>75.0 kg to \<=120.0 kg of weight were included in Cohort 2.0 / 320 / 321 / 32

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 45 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
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.

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