Agitation in Adolescents and Young Adults With ASDPhase 2CALM 201NCT05163717
INP105 Proof-of-concept Study for the Acute Treatment of Agitation in Adolescents and Young Adults With ASD
A Phase 2 study testing INP105 in people with Agitation in Adolescents and Young Adults With ASD, run by Impel Pharmaceuticals at 2 sites in United States.
Trial summary
This is a Phase 2a, proof-of concept, 2-way, 2-period crossover, double-blind study to evaluate the safety and efficacy of INP105 as an acute treatment versus placebo in adolescents and young adults with autism spectrum disorder (ASD) experiencing agitation. Read more about this study
- Who is it for?
- Ages 12 to 21 years
- Conditions the study is for
- Agitation in Adolescents and Young Adults With ASD
- What is being tested?
- INP105
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Jun 2022to 24 Apr 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Confirmed autism spectrum disorder diagnosis
- Admitted as an inpatient to a behavioral unit prior to informed consent
- Displays episodes of moderate to severe agitation
Who cannot join
- Hypersensitivity to olanzapine
- History of severe head trauma, stroke, endocrine disorder, or cardiovascular disease
- History of hypotension
- Currently on a chronic dose of olanzapine
- Currently taking ciprofloxacin, enoxacin, fluvoxamine, or carbamazepine
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Maine Behavioral Healthcare
Portland, Maine, 04102
About this study
Official title: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Single Dose, 2-Way, 2-Period Crossover Safety and Exploratory Efficacy Study of INP105 (POD-OLZ) for the Acute Treatment of Agitation in Adolescents and Young Adults With Autism Spectrum Disorder
This is a Phase 2a, proof-of concept, 2-way, 2-period crossover, double-blind study to evaluate the safety and efficacy of INP105 as an acute treatment versus placebo in adolescents and young adults with autism spectrum disorder (ASD) experiencing agitation. Approximately 32 ASD patients who are currently being treated for agitation/aggression at several inpatient units specializing in behavioral treatment will be enrolled.
INP105 is a novel combination product that sprays a powder formulation of olanzapine to the upper nasal space. An earlier formulation showed a similar extent, but faster rate of absorption compared to the approved intramuscular product. In this study, 5 mg of olanzapine or placebo will be delivered nasally by this combination product to moderately or severely agitated participants.
Read more
Participants will undergo several screening assessments, including observation session(s) of episode(s) of agitation resulting from a frustration task (eg, a non-preferred activity). At least one observation session must result in a documented moderate to severe agitation episode prior to the participant being eligible to enroll in the study and be randomized to treatment.
The study will be conducted in 2 phases. A pilot phase will initially enroll at least 6 participants, who will receive both 5 mg INP105 (5 mg olanzapine) and placebo in random order, in the same crossover design as later participants. Participants will be dosed during a documented moderate to severe episode of agitation. Once 6 participants have completed both dosing periods and have at least 48 hours of post-dose safety data collected, a safety and preliminary efficacy analysis will be performed by an independent unblinded statistical group, and a summary report forwarded to a sponsor-led Data and Safety Review Committee (DSRC), who will remain blinded. Enrollment will be paused during the DSRC pilot phase safety and preliminary efficacy results review. Absent any concerning safety signals, the second phase will enroll all remaining participants. The DSRC may suggest revisions to the protocol, and the protocol amended and approved as necessary, prior to further participants being enrolled.
- Being tested
- INP105, Placebo
- Keywords
- agitation, olanzapine, autism
- Medical subject headings
- Psychomotor Agitation, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INP105Combination product
Also called POD-OLZ
A single 5 mg dose of POD-OLZ (Precision Olfactory Delivery [POD®]-olanzapine)
PlaceboCombination product
Also called POD-placebo, POD-PBO
A single dose of POD-placebo (Precision Olfactory Delivery [POD®]-placebo)
| Study group | Role | What they receive |
|---|---|---|
| INP105 | Experimental | POD-olanzapine (INP105), 5 mg, single dose, to be delivered to each participant Receives: Combination Product: INP105 |
| Placebo | Placebo comparator | POD-placebo, single dose, to be delivered to each participant Receives: Combination Product: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events and serious adverse events in the INP105 and placebo groups up to 48 hours post-dose
All adverse events, serious or not, will be recorded from time of dosing with either INP105 or placebo up until 48 hours post-dose, or until the next treatment is given, which ever is sooner.
Measured: From dosing to 48 hours post dosing
Overall incidence of adverse events and serious adverse events in the INP105 and placebo groups
All adverse events will be recorded as treatment emergent from after dosing until the next treatment, or until last study visit, as applicable.
Measured: From dosing to end of follow-up (7 days), or to the start of next blinded treatment (48 hours), as applicable
Secondary outcomes (10)
Change in Agitation-Calmness Evaluation Scale (ACES) score at 30 minutes post-dose
The ACES is a 9 point scale that measures the degree of agitation versus sedation, ranging from a score of 1 "marked agitation" to 4 "normal" to 9 "unable to be aroused".
Measured: Pre-dose to 30 minutes post-dose
Change in Behavioral Activity Rating Scale (BARS) score at 30 minutes post-dose
The BARS is a 7 point scale measuring the degree of agitated behavior, ranging from 1 "difficult or unable to rouse" to 4 "quiet and awake (normal level of activity)" to 7 "violent, requires restraint.
Measured: Pre-dose to 30 minutes post-dose
Change in Overt Aggression Scale (OAS) score at 30 minutes post-dose
The OAS measures the degree of aggression, using 4 categories of aggression, defined as "verbal aggression", "aggression against objects", "aggression against self", and "aggression against other people". The higher a category is rated, the more severe the degree of aggression. The total score is the sum of the scores from the 4 categories.
Measured: Pre-dose to 30 minutes post-dose
Change in Positive and Negative Syndrome Scale - Excited Component (PEC) score at 30 minutes post-dose
The PEC describes 5 behaviors related to negative aspects of excitability; excitement, tension, hostility, uncooperativeness, poor impulse control. The rater scores each of these aspects from 1 (not present) to 7 (extreme), for a total score that can range from 5 to 35.
Measured: Pre-dose to 30 minutes post-dose
Change in irritability behavior frequency counts at 30 minutes post-dose
Persons with autism can often display repetitive behaviors. These repetitive behaviors, such as rocking, hitting, kicking, will be counted pre-dose and during intervals post-dose.
Measured: Pre-dose to 30 minutes post-dose
Clinical Global Impressions - Improvement (CGI-I) score at 30 minutes post-dose
The CGI-I is a 7 point scale that will be used to assess global improvement in the patient's condition on a scale that ranges from 0 "not assessed", 1 "very much improved" to 7 "very much worse".
Measured: Pre-dose to 30 minutes post-dose
Clinical Global Impressions - Efficacy (CGI-E) score at 30 minutes post-dose
The CGI-E is a scale that measures the efficacy of an intervention balanced by any negative side effects. Scores can range from 1 (vast improvement and no side effects) to 16 (unchanged or worse and side effects that outweigh therapeutic effect).
Measured: Pre-dose to 30 minutes post-dose
Change in modified Aberrant Behavior Checklist - Irritability Subscale (ABC-I) score at 60 minutes post-dose
The ABC-I lists15 behaviors, including aggression, tantrums, crying, seen with irritability and these are scored from 0 "absent" to 3 "severe". Score can therefore range from 0 to 45 (worst irritability).
Measured: Pre-dose and at 60 minutes post-dose
Time to reach an ACES score of 4 (normal) post-dosing
The length of time it will take the participant to move from a score of 2 or 1 on the ACES scale to a score of 4 will be determined.
Measured: Dosing until 120 minutes post-dose
Frequency of administering pharmaceutical rescue intervention within 120 minutes after dosing
The frequency of administering any pharmaceutical intervention other than the study intervention from dosing until 120 minutes after dosing will be recorded and compared for INP105 versus placebo.
Measured: Dosing until 120 minutes post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2021
- Study start23 Jun 2022
- Primary completion31 Mar 2023
- Study completion24 Apr 2023
Why it stopped: Busness reason's
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Agitation in Adolescents and Young Adults With ASDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Impel Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephen Shrewsbury, MD, Study chair, Impel PharmaceuticalsCraig Erickson, MD, Principal investigator, Children's Hospital Medical Center, CincinnatiMatthew Siegel, MD, Principal investigator, Maine Behavioral Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05163717
- Sponsor's protocol ID
- INP105-201
- Acronym
- CALM 201
- Status last verified
- Sep 2023
- First submitted
- 1 Dec 2021
- Last updated
- 28 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Shrewsbury SB, Hocevar-Trnka J, Satterly KH, Craig KL, Lickliter JD, Hoekman J. The SNAP 101 Double-Blind, Placebo/Active-Controlled, Safety, Pharmacokinetic, and Pharmacodynamic Study of INP105 (Nasal Olanzapine) in Healthy Adults. J Clin Psychiatry. 2020 Jun 30;81(4):19m13086. doi: 10.4088/JCP.19m13086.
PubMed 32609960
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Single Dose, 2-Way, 2-Period Crossover Safety and Exploratory Efficacy Study of INP105 (POD-OLZ) for the Acute Treatment of Agitation in Adolescents and Young Adults With Autism Spectrum Disorder
- ClinicalTrials.gov ID
- NCT05163717
- Acronym / sponsor ID
- CALM 201 / INP105-201
- Keywords
- agitation, olanzapine, autism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Busness reason's
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Impel PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 23 Jun 2022 (actual)
- Primary completion
- 31 Mar 2023 (actual)
- Study completion
- 24 Apr 2023 (actual)
- First posted
- 20 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2a, proof-of concept, 2-way, 2-period crossover, double-blind study to evaluate the safety and efficacy of INP105 as an acute treatment versus placebo in adolescents and young adults with autism spectrum disorder (ASD) experiencing agitation. Approximately 32 ASD patients who are currently being treated for agitation/aggression at several inpatient units specializing in behavioral treatment will be enrolled.
INP105 is a novel combination product that sprays a powder formulation of olanzapine to the upper nasal space. An earlier formulation showed a similar extent, but faster rate of absorption compared to the approved intramuscular product. In this study, 5 mg of olanzapine or placebo will be delivered nasally by this combination product to moderately or severely agitated participants.
Participants will undergo several screening assessments, including observation session(s) of episode(s) of agitation resulting from a frustration task (eg, a non-preferred activity). At least one observation session must result in a documented moderate to severe agitation episode prior to the participant being eligible to enroll in the study and be randomized to treatment.
The study will be conducted in 2 phases. A pilot phase will initially enroll at least 6 participants, who will receive both 5 mg INP105 (5 mg olanzapine) and placebo in random order, in the same crossover design as later participants. Participants will be dosed during a documented moderate to severe episode of agitation. Once 6 participants have completed both dosing periods and have at least 48 hours of post-dose safety data collected, a safety and preliminary efficacy analysis will be performed by an independent unblinded statistical group, and a summary report forwarded to a sponsor-led Data and Safety Review Committee (DSRC), who will remain blinded. Enrollment will be paused during the DSRC pilot phase safety and preliminary efficacy results review. Absent any concerning safety signals, the second phase will enroll all remaining participants. The DSRC may suggest revisions to the protocol, and the protocol amended and approved as necessary, prior to further participants being enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| INP105 | Experimental | Combination Product: INP105POD-olanzapine (INP105), 5 mg, single dose, to be delivered to each participant |
| Placebo | Placebo comparator | Combination Product: PlaceboPOD-placebo, single dose, to be delivered to each participant |
Who may qualify
- Ages
- 12 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Confirmed autism spectrum disorder diagnosis
- Admitted as an inpatient to a behavioral unit prior to informed consent
- Displays episodes of moderate to severe agitation
Key exclusion criteria (5 listed)
- Hypersensitivity to olanzapine
- History of severe head trauma, stroke, endocrine disorder, or cardiovascular disease
- History of hypotension
- Currently on a chronic dose of olanzapine
- Currently taking ciprofloxacin, enoxacin, fluvoxamine, or carbamazepine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INP105Also: POD-OLZA single 5 mg dose of POD-OLZ (Precision Olfactory Delivery [POD®]-olanzapine) | Combination product | INP105 |
| PlaceboAlso: POD-placebo, POD-PBOA single dose of POD-placebo (Precision Olfactory Delivery [POD®]-placebo) | Combination product | Placebo |
Primary outcome
Incidence of adverse events and serious adverse events in the INP105 and placebo groups up to 48 hours post-dose
Time frame: From dosing to 48 hours post dosing
All adverse events, serious or not, will be recorded from time of dosing with either INP105 or placebo up until 48 hours post-dose, or until the next treatment is given, which ever is sooner.
Overall incidence of adverse events and serious adverse events in the INP105 and placebo groups
Time frame: From dosing to end of follow-up (7 days), or to the start of next blinded treatment (48 hours), as applicable
All adverse events will be recorded as treatment emergent from after dosing until the next treatment, or until last study visit, as applicable.
10 secondary outcomes
Change in Agitation-Calmness Evaluation Scale (ACES) score at 30 minutes post-dose
Time frame: Pre-dose to 30 minutes post-dose
Change in Behavioral Activity Rating Scale (BARS) score at 30 minutes post-dose
Time frame: Pre-dose to 30 minutes post-dose
Change in Overt Aggression Scale (OAS) score at 30 minutes post-dose
Time frame: Pre-dose to 30 minutes post-dose
Change in Positive and Negative Syndrome Scale - Excited Component (PEC) score at 30 minutes post-dose
Time frame: Pre-dose to 30 minutes post-dose
Change in irritability behavior frequency counts at 30 minutes post-dose
Time frame: Pre-dose to 30 minutes post-dose
Clinical Global Impressions - Improvement (CGI-I) score at 30 minutes post-dose
Time frame: Pre-dose to 30 minutes post-dose
Clinical Global Impressions - Efficacy (CGI-E) score at 30 minutes post-dose
Time frame: Pre-dose to 30 minutes post-dose
Change in modified Aberrant Behavior Checklist - Irritability Subscale (ABC-I) score at 60 minutes post-dose
Time frame: Pre-dose and at 60 minutes post-dose
Time to reach an ACES score of 4 (normal) post-dosing
Time frame: Dosing until 120 minutes post-dose
Frequency of administering pharmaceutical rescue intervention within 120 minutes after dosing
Time frame: Dosing until 120 minutes post-dose
Results and safety
The study was stopped early (reason given: Busness reason's). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Background: PubMed 32609960Shrewsbury SB, Hocevar-Trnka J, Satterly KH, Craig KL, Lickliter JD, Hoekman J. The SNAP 101 Double-Blind, Placebo/Active-Controlled, Safety, Pharmacokinetic, and Pharmacodynamic Study of INP105 (Nasal Olanzapine) in Healthy Adults. J Clin Psychiatry. 2020 Jun 30;81(4):19m13086. doi: 10.4088/JCP.19m13086.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Shrewsbury, MD study chair
Impel Pharmaceuticals
Craig Erickson, MD principal investigator
Children's Hospital Medical Center, Cincinnati
Matthew Siegel, MD principal investigator
Maine Behavioral Healthcare
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing INP105 in people with Agitation in Adolescents and Young Adults With ASD, run by Impel Pharmaceuticals at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Busness reason's). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events and serious adverse events in the INP105 and placebo groups up to 48 hours post-dose (time frame: From dosing to 48 hours post dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05163717, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.