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

A Randomized, Open-label, Two-treatment, Two-period, Single-dose, Crossover Study to Evaluate the Bioavailability of Teduglutide Administered Subcutaneously by Syringe Injection Versus Pen Injector in Healthy Adult Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Teduglutide; Device: Syringe Injection; Device: Pen injector

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Teduglutide; 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.; Other Names: TAK-633; Device: Syringe Injection; Teduglutide was administered using syringe.; Device: Pen injector; Teduglutide was administered using pen injector.
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.	Drug: Teduglutide; 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.; Other Names: TAK-633; Device: Syringe Injection; Teduglutide was administered using syringe.; Device: Pen injector; Teduglutide was administered using pen injector.
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.	Drug: Teduglutide; 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.; Other Names: TAK-633; Device: Syringe Injection; Teduglutide was administered using syringe.; Device: Pen injector; Teduglutide was administered using pen injector.
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.	Drug: Teduglutide; 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.; Other Names: TAK-633; Device: Syringe Injection; Teduglutide was administered using syringe.; Device: Pen injector; Teduglutide was administered using pen injector.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Cmax is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.	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		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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	Cmax of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported.	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	AUC0-infinity of teduglutide by injection site (i.e., thigh, abdomen, and arm) was assessed and reported.	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		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	CL/F for extravascular administration divided by the fraction of dose absorbed of teduglutide was assessed and reported.	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 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.	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
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.	From the start of study drug administration up to follow-up (up to 42 days)
Number of Participants With Clinically Significant Change in Vital Signs	Vital signs included body temperature, respiratory rate, blood pressure, and heart rate.	From the start of study drug administration up to follow-up (up to 42 days)
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.	From the start of study drug administration up to follow-up (up to 42 days)
Number of Participants With Clinically Significant Changes in Physical Examinations	Physical examination included examination of respiratory, cardiovascular, and gastrointestinal system.	From the start of study drug administration up to follow-up (up to 42 days)
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.	Day 1

Collaborators and Investigators

• Sponsor: Shire
• Collaborators: Takeda Development Center Americas, Inc.

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2021
• Primary Completion (Actual): August 20, 2021
• Study Completion (Actual): August 20, 2021

Study Registration Dates

• First Submitted: July 7, 2020
• First Submitted That Met QC Criteria: July 7, 2020
• First Posted (Actual): July 10, 2020

Study Record Updates

• Last Update Posted (Actual): October 4, 2022
• Last Update Submitted That Met QC Criteria: March 29, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Gastrointestinal Agents; Protective Agents; Radiation-Protective Agents; Teduglutide
• Other Study ID Numbers: TAK-633-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No