ADASUVE-Lorazepam Drug-Drug Interaction

NCT01877642 | Completed Phase 4 Results FDA Drug

• 1 other identifier: AMDC-204-402
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This study will compare the safety and effects over time for giving both ADASUVE and lorazepam (intramuscular) compared to that of each agent given alone.

Conditions

Healthy Volunteers

Keywords

ADASUVE; inhaled loxapine; drug drug interaction; lorazepam; acute treatment of agitation

Outcome Measures

Primary Outcomes (2)

• Maximum Level of Sedation for Lorazepam 1 mg IM + ADASUVE 10 mg

  Determine the maximum level of sedation for Lorazepam 1 mg IM + ADASUVE 10 mg based on the 100 mm Visual Analog Scale (VAS) ranging from (0=sleepy to 100=wide awake)

  24 hours

• Relative Pharmacodynamic Effect on Respiration Rate for Combined vs Individual (Lorazepam, Loxapine)

  LS Mean ratio (90% CI) of the area under the curve for 0 to 24 hours (AUC 0-24) for respiration rate following administration of Lorazepam+Loxapine compared to the same measure following each control drug given alone (Lorazepam, Loxapine)

  24 hours

Secondary Outcomes (6)

• Relative Pharmacodynamic Effect on Systolic Blood Pressure for Combined vs Individual (Lorazepam, Loxapine)

  24 hours

• Relative Pharmacodynamic Effect on Sedation for Combined vs Individual (Lorazepam, Loxapine)

  24 hours

• Relative Pharmacodynamic Effect on Pulse Oximetry for Combined vs Individual (Lorazepam, Loxapine)

  24 hours

• Relative Pharmacodynamic Effect on Heart Rate for Combined vs Individual (Lorazepam, Loxapine)

  24 hours

• Relative Pharmacodynamic Effect on Diastolic Blood Pressure for Combined vs Individual (Lorazepam, Loxapine)

  24 hours

Study Arms (7)

Open Label (lorazepam 1 mg + Inhaled loxapine 10 mg)

OTHER

Inhaled Staccato loxapine 10 mg + IM lorazepam 1 mg to confirm tolerability of combined treatment

Drug: Lorazepam 1 mg IM; Drug: Inhaled loxapine 10 mg

Treatment Sequence ABC

OTHER

Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg

Drug: Lorazepam 1 mg IM; Drug: Inhaled loxapine 10 mg; Drug: Inhaled Placebo; Drug: Placebo IM

Treatment Sequence ACB

OTHER

Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg

Drug: Lorazepam 1 mg IM; Drug: Inhaled loxapine 10 mg; Drug: Inhaled Placebo; Drug: Placebo IM

Treatment Sequence BCA

OTHER

Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg

Drug: Lorazepam 1 mg IM; Drug: Inhaled loxapine 10 mg; Drug: Inhaled Placebo; Drug: Placebo IM

Treatment Sequence BAC

OTHER

Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg

Drug: Lorazepam 1 mg IM; Drug: Inhaled loxapine 10 mg; Drug: Inhaled Placebo; Drug: Placebo IM

Treatment Sequence CAB

OTHER

Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg

Drug: Lorazepam 1 mg IM; Drug: Inhaled loxapine 10 mg; Drug: Inhaled Placebo; Drug: Placebo IM

Treatment Sequence CBA

OTHER

Treatment: A = Lorazepam 1 mg IM + inhaled placebo, B = Lorazepam 1 mg IM + inhaled loxapine 10 mg, C= Placebo IM + inhaled loxapine 10 mg

Drug: Lorazepam 1 mg IM; Drug: Inhaled loxapine 10 mg; Drug: Inhaled Placebo; Drug: Placebo IM

Interventions

Lorazepam 1 mg IM DRUG

Lorazepam 1 mg intramuscular

Also known as: Ativan 1 mg IM

Open Label (lorazepam 1 mg + Inhaled loxapine 10 mg); Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Inhaled loxapine 10 mg DRUG

Inhaled Staccato loxapine 10 mg

Also known as: ADASUVE 10 mg

Open Label (lorazepam 1 mg + Inhaled loxapine 10 mg); Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Inhaled Placebo DRUG

Inhaler with no drug in it to mimic the ADASUVE inhaler

Also known as: Staccato Placebo

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Placebo IM DRUG

intramuscular placebo to mimic lorazepam 1 mg IM

Also known as: Saline

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects between the ages of 18 to 50 years, inclusive.
• Body mass index (BMI) ≥18 and ≤32.
• Subjects who are willing and able to comply with the study schedule and requirements, and stay at the CRU for 9 days.
• Subjects who speak, read, and understand English and are willing and able to provide written informed consent on an IRB approved form prior to the initiation of any study procedures.
• Subjects who are in good general health prior to study participation as determined by a detailed medical history, physical examination, 12-lead ECG, blood chemistry profile, hematology, urinalysis, and in the opinion of the Principal Investigator.
• Female participants (if of child-bearing potential and sexually active) who agree to use a medically acceptable and effective birth control method throughout the study and for 30 days following the end of the study
• Male participants (if sexually active with a partner of child-bearing potential) who agree to use a medically acceptable and effective birth control method from the first dose and for 90 days following last dose of study drug. Male participants must refrain from donating sperm for the same period.

You may not qualify if:

• Subject history, which includes: any cardiovascular disease or disorder; asthma, chronic obstructive lung disease, or any use of an inhaler prescribed for wheezing or bronchospasm must be excluded; sleep apnea; acute narrow-angle glaucoma; any neurological, gastrointestinal, hepatic, renal, hematologic, endocrine and/or metabolic disease or disorder; psychiatric illness or mental disorder except for short term situational anxiety or depression of \< 2 years duration; any substance abuse or addiction within the last 2 years; pregnancy within the past 6 months.
• Subjects who have taken prescription or nonprescription medication within 7 days of Visit 2.
• Subjects who have had an acute illness within the last 7 days of Visit 2.
• Subjects who have a history of HIV positivity.
• Subjects who test positive for alcohol or have a positive urine drug screen.
• Subjects who have a history of allergy or intolerance to loxapine or amoxapine.
• Subjects who have a history of allergy or intolerance to lorazepam or any other benzodiazepine.
• Subjects who have a history of allergy or intolerance to polyethylene glycol, propylene glycol, or benzyl alcohol
• Female subjects who have a positive pregnancy test at screening or at admission to Visit 2, or are breastfeeding.
• Subjects who have received an investigational drug within 30 days prior to the Screening Visit.
• Subjects who have any other disease(s), by history, physical examination, or laboratory abnormalities that, in the investigator's opinion, presents undue risk to the subject or may confound the interpretation of study results.
• Subjects who are considered by the investigator, for any reason, to be an unsuitable candidate for receiving lorazepam or ADASUVE.

Sponsors & Collaborators

• Alexza Pharmaceuticals, Inc.: lead

Study Sites (1)

Covance-Evansville

Evansville, Indiana, 47710, United States

Location

Related Publications (1)

• Spyker DA, Cassella JV, Stoltz RR, Yeung PP. Inhaled loxapine and intramuscular lorazepam in healthy volunteers: a randomized placebo-controlled drug-drug interaction study. Pharmacol Res Perspect. 2015 Dec 17;3(6):e00194. doi: 10.1002/prp2.194. eCollection 2015 Dec.

  PMID: 27022468 RESULT

MeSH Terms

Interventions

Lorazepam; Loxapine; Sodium Chloride

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dibenzoxazepines; Heterocyclic Compounds, 3-Ring; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

The 1-mg IM lorazepam dose used in this study was lower than that used in some previous studies assessing the effects of concomitant administration of antipsychotics with up to 2-mg lorazepam for the treatment of agitation.

Results Point of Contact

• Title: Executive VP, Research & Development, Regulatory & Quality
• Organization: Alexza Pharmaceuticals, Inc

ClinicalTrialsInfo@alexza.com

650.944.7777

Study Officials

• Randall R Stoltz, MD

  Medical Director, Covance-Evansville, Evansville, IN 47710

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2013
• First Posted: June 14, 2013
• Study Start: June 1, 2013
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: December 13, 2017
• Results First Posted: December 13, 2017

Record last verified: 2013-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)