Blood Oxygen Level Dependent (BOLD) Signal by Functional Magnetic Resonance Imaging (fMRI) Visual Nauseogenic Task
| Group | Value |
|---|---|
| Albiglutide 50 mg | not posted |
| Exenatide 10 µg | not posted |
| Off-therapy MRI | not posted |
Trial · Interventional
TerminatedPhase 4Results postedRegistry dataThis trial was stopped early.
The registry gives no reason.
Results were posted for this trial.
United States
1 trial · 1 stopped early · 1 with posted results
A Study Comparing the Effect of Albiglutide With Exenatide on Regional Brain Activity Related to Nausea in Healthy Subjects
NCT0280251420 Sept 2016 to 7 Sept 2017
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
The drug effects will be studied after a single dose of 50 milligram (mg) albiglutide and a single dose of 10 microgram exenatide, to gain insight into the central mechanisms of nausea associated with Glucagon-like peptide-1 receptor (GLP-1R) agonists. This study will explore the potential differences at the expected time of maximum concentration (Cmax) between a long-acting (albiglutide) and short-acting (exenatide) GLP-1R agonist in brain activation of healthy volunteers assessed by magnetic resonance imaging (MRI). This is a phase IV, 2-part, 2-period crossover (session), single dose, randomized, single blind (blinded to both the subject and the imaging evaluators analysing the MRI data), placebo- and active-controlled study in adult healthy volunteers who are susceptible to motion sickness. Part A and Part B are the same in design, both consisting of a screening stage, a dosing/assessment stage, and a follow-up visit. Data from Part A will inform progression, methods, and analysis plan for Part B. Each sequence includes three scanning visits: albiglutide plus scan, exenatide plus scan and an off-therapy -natural history scan with a 6-9 week washout period between the dosing scans. A total of 24 to 28 subjects will be randomized in the study (Part A and Part B). The cross over design is divided into 2 sessions and schedule is as follow, on Day 1 (either Session 1 (S1) or Session 2 (S2) per, if randomized) subject will under go an off-therapy MRI scan, on Day 5 subject will receive a single dose of 50 mg albiglutide or albiglutide placebo, and Day 8 subject will receive a single dose of 10 microgram exenatide or saline placebo followed by a post-dose MRI scan. At each session subject will receive only one active drug (albiglutide or exenatide).
Experimental
With Off therapy MRI in S1:Albiglutide-S1 & Exenatide-S2
In session 1, eligible subject will undergo off-therapy MRI scan Subject will receive single dose each of 50 mg albiglutide on Day 5 and exenatide placebo on Day 8 followed by a post-dose MRI. In session 2, subject will receive single dose each of albiglutide placebo on Day 1 (Week 9) and 10 microgram exenatide on Day 4 followed by a post-dose MRI scan. There will be 6-9 week washout period between Session 1 and Session 2
Experimental
Without Off therapy MRI in S1:Albiglutide-S1 & Exenatide-S2
In session 1, eligible subject will receive single dose each of 50 mg albiglutide on Day 1 and exenatide placebo on Day 4 followed by a post-dose MRI scan. In session 2, Day 1 (Week 9) subject will undergo off-therapy MRI scan. Subject will receive single dose each of albiglutide placebo on Day 5 and 10 microgram of exenatide on Day 8 followed by a post-dose MRI scan. There will be 6-9 week washout period between Session 1 and Session 2
Experimental
With Off therapy MRI in S1:Exenatide-S1 & Albiglutide-S2
In session 1, Day 1 subject will undergo off-therapy MRI scan Subject will receive single dose each of albiglutide placebo on Day 5 and 10 microgram of exenatide on Day 8 followed by a post-dose MRI scan In session 2, eligible subject will receive single dose each of 50 mg albiglutide on Day 1 (Week 9) and exenatide placebo Day 4 followed by a post-dose MRI scan. There will be 6-9 week washout period between Session 1 and Session 2
Experimental
Without Off therapy MRI in S1: Exenatide-S1 & Albiglutide-S2
In session 1, subject will receive single dose each of albiglutide placebo on Day 1 and 10 microgram exenatide on Day 4 followed by a post-dose MRI scan. In session 2, subject will undergo off-therapy MRI scan on Day 1 (Week 9). Subject will receive single dose each of 50 mg albiglutide on Day 5 and exenatide placebo on Day 8 followed by a post-dose MRI scan.. There will be 6-9 week washout period between Session 1 and Session 2
Outcomes the sponsor listed as primary.
Blood Oxygen Level Dependent (BOLD) Signal by Functional Magnetic Resonance Imaging (fMRI) Visual Nauseogenic Task
Time frame · Up to Week 11
BOLD signal fMRI Visual Nauseogenic Task data were to be collected at indicated time-points. The seed-to-voxel driven approach included a priori seed Regions of interest (ROIs) placed in brain areas subserving nausea-related processing included regions like interoceptive/sensory (insula, Dorsal anterior cingulate cortex \[dACC\]), emotional/affective (amygdala, Pregenual anterior cingulate cortex \[pgACC\]), and cognitive/evaluative (dorsolateral prefrontal cortex \[dlPFC\]/ Occipitofrontal Circumference \[OFC\]) brain areas, primary visual (V1) and extrastriate cortices. The primary endpoints of this exploratory study involved combining data from Part A and Part B. The purpose of Part A was decision making for Part B. Placebo was used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was to be reported in albiglutide, exenatide and off-therapy arms only.
Regional Cerebral Blood Flow (rCBF) by Functional MRI (fMRI)-Arterial Spin Labeling (ASL)
Time frame · Up to Week 11
Pseudo-Continuous Arterial spin labeling (pCASL) data were planned to be analyzed to assess rCBF within the brain during using functional MRI scans. Quality control of imaging data were planned to be performed by visual inspection with adequate data denoted by mean rCBF values over the gray matter within a previously defined normal range (i.e., 40-60 millimeter \[mm\]/100 gram \[g\] tissue/ minute \[min\]). In addition, all data were planned to undergo motion and physiological noise correction. Placebo was used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.
Glutamate Concentration in Nausea-associated Brain Regions by Magnetic Resonance Spectroscopy (MRS)
Time frame · Up to Week 11
Glutamine/Glutamate (Glx) was planned to be analyzed using proton-density weighted magnetic resonance spectroscopy (1H-MRS). 1H-MRS analysis assessed regional differences in Glx concentrations, normalized as a ratio with creatine. MRS quantification of metabolites of interest were based on frequency domain analysis using a Linear Combination of Model spectra (LCModel). Cramer-Rao lower bounds (CRLBs), as reported from the LCModel analysis, were planned to be used to assess the reliability of the major metabolites and adequate Signal to noise ratio (SNR). CRLBs values less than 40% were further planned to be analyzed. Metabolite maps for each participant, and each session were planned to be calculated. Placebo was used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.
Gama-aminobutyric Acid (GABA) Concentration in Nausea-associated Brain Regions by MRS
Time frame · Up to Week 11
GABA concentrations was planned to be analyzed using proton-density weighted 1H-MRS. 1H-MRS analysis assessed regional differences GABA concentrations, normalized as a ratio with creatine. MRS quantification of metabolites of interest were based on frequency domain analysis using a LC Model. CRLBs, as reported from the LC Model analysis, were planned to be used to assess the reliability of the major metabolites and adequate SNR. CRLBs values less than 40% were further planned to be analyzed. Metabolite maps for each participant, and each session were planned to be calculated. Placebo was used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.
Heart Rate Variability Using Autonomic Response Measures by MRI
Time frame · Up to Week 11
Heart rate variability was to be evaluated using autonomic response measure. All peripheral autonomic physiological signals were planned to be collected at 400 Hz using Chart Data Acquisition Software (ADInstruments) on a laptop equipped with a 16-channel Powerlab DAQ System (ADInstruments). Heart rate variability was to be reported as recorded by chart data acquisition software. Placebo was planned to be used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.
Number of Participants With Abnormal Electrocardiogram (ECG) Intervals Using Autonomic Response Measures by MRI
Time frame · Up to Week 11
ECGs intervals were to be evaluated for the participant during the scanning session using autonomic response measures. ECG signal were planned to be collected with an MRI-compatible participant Monitoring system (Biopac 150, Biopac Systems Inc.) through MRI-compatible electrodes (VerMed, Bellows Falls) placed on the chest. Placebo was planned to be used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.
Number of Participants With Abnormal Respiratory Rate Using Autonomic Response Measures by MRI
Time frame · Up to Week 11
Number of participants with abnormal respiratory rate are reported during imaging session was to be evaluated using autonomic response measures. All peripheral autonomic physiological signals were planned to be collected at 400 Hz using Chart Data Acquisition Software (ADInstruments) on a laptop equipped with a 16-channel Powerlab DAQ System (ADInstruments). Placebo was planned to be used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.
Number of Participants With Skin Conductance Level Using Autonomic Response Measures by MRI
Time frame · Up to Week 11
Skin conductance level was to planned to be evaluated with MRI-compatible bipolar Silver (Ag)/Silver chloride (AgCl) finger electrodes placed on the palmar aspect of the second and fourth fingers of the non-dominant (left) hand, prior to the MRI session. All peripheral autonomic physiological signals were planned to be collected at 400 Hz using Chart Data Acquisition Software (ADInstruments) on a laptop equipped with a 16-channel Powerlab DAQ System (ADInstruments). Placebo was planned to be used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.
Number of Participants With Abnormal Heart Rate for Session 1
Time frame · Day 1: pre-MRI, 0.5 hour post-MRI; Day 4: -2 hours pre-MRI, 0.5 and 1 hour post MRI; Day 5; Day 8: -2 hour pre-MRI, 0.5 and 1 hour post-MRI
Data of participants with abnormal heart rate (measured during site visits by sphygmomanometer) were reported. Participants with low and high heart rate has been presented. Potential clinical concern value for heart rate is \< 50 beats per minute to \> 120 beats per minute. Safety Population comprised of all participants who received at least one dose of the study treatment.
Number of Participants With Abnormal Heart Rate for Session 2
Time frame · Day 1: pre-MRI, 0.5 hour post-MRI; Day 4: -2 hours pre-MRI, 0.5 and 1 hour post MRI; Day 5; Day 8: -2 hour pre-MRI, 0.5 and 1 hour post-MRI
Data of participants with abnormal heart rate (measured during site visits by sphygmomanometer) were reported. Participants with low and high heart rate has been presented. Potential clinical concern value for heart rate is \< 50 beats per minute to \> 120 beats per minute.
Number of Participants With Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Session 1
Time frame · Day 1: pre-MRI, 0.5 hour post-MRI; Day 4: -2 hours pre-MRI, 0.5 and 1 hour post MRI; Day 5; Day 8: 0.5 and 1 hour post-MRI
SBP and DBP were measured in supine position after 5 minutes rest. Data for Session 1 and 2 and for Pre and Post MRI has been presented. Potential clinical concern value for SBP is \<100 millimeters of mercury (mmHg) and \>170 mmHg. Potential clinical concern value for DBP is \<50 mmHg and \>110 mmHg.
Number of Participants With Abnormal SBP and DBP for Session 2
Time frame · Day 1: pre-MRI, 0.5 hour post-MRI; Day 4: -2 hours pre-MRI, 0.5 and 1 hour post MRI; Day 5; Day 8: 0.5 and 1 hour post-MRI
SBP and DBP were measured in supine position after 5 minutes rest. Data for Session 1 and 2 and for Pre and Post MRI has been presented. Potential clinical concern value for SBP is \<100 millimeters of mercury (mmHg) and \>170 mmHg. Potential clinical concern value for DBP is \<50 mmHg and \>110 mmHg.
Number of Participants With Abnormal Clinical Chemistry Parameters
Time frame · Up to Week 11
Clinical chemistry parameters included assessment of blood urea nitrogen (BUN), creatinine, epidermal growth factor receptor (eGRF), potassium, sodium, calcium, Aspartate transaminase (AST), Alanine transaminase (AST), Alkaline phosphatase, total and direct bilirubin, total protein and albumin.
Number of Participants With Abnormal Hematology Parameters
Time frame · Up to Week 11
Hematology parameters included assessment of platelet count, red blood cell (RBC) count, hemoglobin, hemotocrit, RBC indices including mean corpuscular volume and mean corpuscular hemoglobin (MCH), and White blood cells (WBC) count with differential count including, neutrophils, lymphocytes, monocytes, eosinophils and basophils.
Number of Participants With Abnormal Urinalysis
Time frame · Up to Week 11
Urinalysis parameters included assessment of specific gravity, microscopic analysis, and potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick method.
Number of Participants With Abnormal Glycemic Parameters
Time frame · Up to Week 11
Glycemic parameters included assessment of capillary blood glucose and fasting plasma glucose.
Number of Participants With Non-serious Adverse Events (AE) With Incidence > = 2 % and Serious AEs (SAE)
Time frame · Up to Week 13
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE. Data of participants with non-serious AEs ( with incidence \>= 2%) and SAEs has been presented. Placebo was included to maintain the single blind only; similar to double dummy.
Nausea Ratings Scale to Rate Nausea Sensation Using Autonomic Response Measures by MRI
Time frame · Up to Week 11
Nausea ratings were planned to be collected during motion sickness provocation using a 0-4 numerical rating scale (NRS), where 1 is rated as minimal nausea experienced and 4 as severe nausea was experienced. Participants were asked to press buttons on a MRI compatible button-box to rate nausea from 0 to 4. Placebo was planned to be used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.
Gastrointestinal (GI) Visual Analogue Scale (VAS) for Assessment of Nausea for Session 1
Time frame · Day 1 (Pre-MRI and 0.5 hour post-MRI); Day 4 (Pre-MRI and 0.5 hour post-MRI); and Day 8 (Pre-MRI and 0.5 hour post-MRI)
Participant completed VAS to record their perception of stomach fullness, hunger, nausea, bloating and abdominal pain. The VAS was represented by lines, 100 millimeter in length, anchored with words describing the most negative rating on the left and the most positive rating on the right. Scores ranged from 0 mm to 100 mm. Scores of 0 mm are worst (most negative rating on the left) and scores of 100 mm are best (most positive rating on the right). NA indicates that data were not available as standard deviation could not be calculated due to low number of participants.
GI VAS for Assessment of Nausea for Session 2
Time frame · Day 1 (Pre-MRI and 0.5 hour post-MRI); Day 4 (Pre-MRI and 0.5 hour post-MRI); and Day 8 (Pre-MRI and 0.5 hour post-MRI)
Participant completed VAS to record their perception of stomach fullness, hunger, nausea, bloating and abdominal pain. The VAS was represented by lines, 100 millimeter in length, anchored with words describing the most negative rating on the left and the most positive rating on the right. Scores ranged from 0 mm to 100 mm. Scores of 0 mm are worst (most negative rating on the left) and scores of 100 mm are best (most positive rating on the right). NA indicates that data were not available as standard deviation could not be calculated due to low number of participants.
Motion Sickness Assessment Questionnaire (MSAQ) for Assessment of Nausea for Session 1
Time frame · Day 1 0.5 hour post-MRI; Day 4 0.5 hour post-MRI; and Day 8 0.5 hour post-MRI
Participant completed MSAQ to quantify the severity of different dimensions of nausea induced by motion sickness. There were total 16 items: 4 related to gastro-intestinal (GI), 5 related to central (C), 3 related to peripheral (P) and 4 related to sopite-related (SR). All items were scored individually on a scale of 1-9 where 1 means 'not at all severe' and 9 means 'severe', with higher score indicates more severity. Individual 16 items with their scores are presented. NA indicates that data were not available as standard deviation could not be calculated due to low number of participants.
MSAQ for Assessment of Nausea for Session 2
Time frame · Day 1 0.5 hour post-MRI; Day 4 0.5 hour post-MRI; and Day 8 0.5 hour post-MRI
Participant completed MSAQ to quantify the severity of different dimensions of nausea induced by motion sickness. There were total 16 items: 4 related to gastro-intestinal (GI), 5 related to central (C), 3 related to peripheral (P) and 4 related to sopite-related (SR). All items were scored individually on a scale of 1-9 where 1 means 'not at all severe' and 9 means 'severe', with higher score indicates more severity. Individual 16 items with their scores are presented. NA indicates that data were not available as standard deviation could not be calculated due to low number of participants.
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
| Group | Value |
|---|---|
| Albiglutide 50 mg | not posted |
| Exenatide 10 µg | not posted |
| Off-therapy MRI | not posted |
| Group | Value |
|---|---|
| Albiglutide 50 mg | not posted |
| Exenatide 10 µg | not posted |
| Off-therapy MRI | not posted |
| Group | Value |
|---|---|
| Albiglutide 50 mg | not posted |
| Exenatide 10 µg | not posted |
| Off-therapy MRI | not posted |
| Group | Value |
|---|---|
| Albiglutide 50 mg | not posted |
| Exenatide 10 µg | not posted |
| Off-therapy MRI | not posted |
| Group | Value |
|---|---|
| Albiglutide 50 mg | not posted |
| Exenatide 10 µg | not posted |
| Off-therapy MRI | not posted |
| Group | Value |
|---|---|
| Albiglutide 50 mg | not posted |
| Exenatide 10 µg | not posted |
| Off-therapy MRI | not posted |
| Group | Value |
|---|---|
| Albiglutide 50 mg | not posted |
| Exenatide 10 µg | not posted |
| Off-therapy MRI | not posted |
| Group | Value |
|---|---|
| Albiglutide 50 mg | not posted |
| Exenatide 10 µg | not posted |
| Off-therapy MRI | not posted |
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Albiglutide 50 mgParticipants received albiglutide 50 mg on Day 5 and exenatide placebo on Day 8 or albiglutide 50 mg on Day 1 and exenatide placebo on Day 4 during session 1 or 2 as per randomization. The timing of the albiglutide dose and post-dose MRI were based on the Tmax of albiglutide. Hence, the Day 4 and Day 8 post dose MRI served as the post-albiglutide dose MRI in this study and the exenatide placebo served to preserve the study blinding. | 0 / 4 | 0 / 4 | 1 / 4 |
| Exenatide 10 µgParticipants received albiglutide matching placebo on Day 5 and exenatide 10 μg on Day 8 or albiglutide matching placebo on Day 1 and exenatide 10 μg on Day 4 during session 1 or 2 as per randomization schedule. The timing of the exenatide dose and post-dose MRI were based on the Tmax of exentatide. Hence, the Day 4 and Day 8 post dose MRI served as the post exenatide dose MRI and the albiglutide matching placebo served to preserve the study blind. | 0 / 4 | 0 / 4 | 0 / 4 |
| Albiglutide Matching PlaceboParticipants in Session 1 received albiglutide matching placebo on Day 1 and during Session 2 participants received albiglutide matching placebo on Day 5. There was a wash-out period of 6-9 weeks between the two sessions. | 0 / 4 | 0 / 4 | 0 / 4 |
| Exenatide Matching PlaceboParticipants in Session 1 received exenatide matching placebo on Day 4 and during Session 2 participants received exenatide matching placebo on Day 8. There was a wash-out period of 6-9 weeks between the two sessions. | 0 / 4 | 0 / 4 | 0 / 4 |
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