A Switch Study From High-Sodium Oxybate to XYWAV to Evaluate Changes in Blood Pressure in Participants With Narcolepsy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Jazz Pharmaceuticals PLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

14 Jun 2024 → 10 Mar 2025

Decision date (initial)

2023-11-14

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-504892-25-00

ClinicalTrials.gov

NCT05869773

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the impact of switching from twice-nightly high-sodium oxybate to XYWAV on 24-hour ambulatory SBP for participants with narcolepsy

Secondary objectives 3

1. To evaluate the impact of switching from twice-nightly high-sodium oxybate to XYWAV on daytime ambulatory Systolic blood pressure for participants with narcolepsy
2. To evaluate the impact of switching from twice-nightly high-sodium oxybate to XYWAV on seated resting Systolic blood pressure for participants with narcolepsy
3. To evaluate the impact of switching from twice-nightly high-sodium oxybate to XYWAV on night-time Systolic blood pressure (SBP) for participants with narcolepsy

Conditions and MedDRA coding

Narcolepsy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participants must be 18 to 70 years of age inclusive, at the time of signing the informed consent.
2. Participants have a documented diagnosis of Type 1 or Type 2 narcolepsy that meets ICSD-3 or DSM-5 criteria.
3. Participants must have been receiving a total dose of high-sodium oxybate (eg, XYREM) of 6 to 9 g/night (inclusive) with twice-nightly dosing for a minimum of 6 consecutive weeks prior to screening.
4. If currently treated with stimulants and/or alerting agents or other medications known to affect Blood Pressure, participant must have been taking the same dosing regimen for at least 2 months prior to screening and agree to take the same dose throughout the study.
5. If currently taking stable doses of antihypertensive therapies, participant must maintain these treatments at the same dose throughout the study unless otherwise advised by their medical care provider. Also refer to exclusion criterion 12.
6. Participant’s average screening SBP must be between 130 and 155 mm Hg (inclusive). Note: BP measurements will be collected using a device provided by the sponsor as described in Section 8.3.2.1. Participants with resistant hypertension are excluded (refer to exclusion criterion 12).
7. Participant’s average screening Diastolic blood pressure (DBP) must not be greater than 95 mm Hg. Note: BP measurements will be collected using a device provided by the sponsor as described in Section 8.3.2.1. Participants with resistant hypertension are excluded (refer to exclusion criterion 12).
8. Participant is male or female. • A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: − Is a woman of nonchildbearing potential OR − Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), preferably with low user dependency, as described in Appendix 4 of the Protocol, during the study intervention period and for at least 7 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention. • A WOCBP must have a negative highly sensitive pregnancy test (serum) as required by local regulations during screening (Section 8.3.5 of the Protocol). • Additional requirements for pregnancy testing during and after study intervention are provided in Section 8.3.5 of the Protocol. • The investigator is responsible for review of medical history, contraception history, menstrual history, and recent sexual activity to decrease the risk of inclusion of a woman with an early undetected pregnancy.

Exclusion criteria 12

1. History or presence of any acutely unstable medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or surgical history that could affect the safety of the participant or interfere with study assessments or the ability of the participant to complete the study based on the judgment of the investigator.
2. Occupation requiring nighttime or variable shift work.
3. Participant was previously eligible for this study but either was terminated early or was discontinued.
4. Presence of significant cardiovascular disease including but not limited to: myocardial infarction within the past year, unstable angina pectoris, symptomatic or hospitalized congestive heart failure (ACC/AHA stage C or D), revascularization procedures within the past year, chronic/persistent atrial fibrillation, ventricular cardiac arrhythmias requiring automatic implantable cardioverter defibrillator or anti-arrhythmic therapy, or any significant cardiovascular condition that in the investigator’s opinion may jeopardize participant safety in the study, including screening ECG results.
5. Presence of atrial fibrillation detected on screening ECG.
6. Current or recent (within the past 2 years) diagnosis of a moderate or severe substance use disorder (excluding caffeine) according to DSM-5 criteria. Nicotine use disorder is excluded only if it impacts sleep (ie, a participant who routinely awakens at night to smoke).
7. History of phenylketonuria or history of hypersensitivity to phenylalanine-derived products.
8. Succinic semi-aldehyde dehydrogenase deficiency by medical history.
9. Received an investigational drug in the past 30 days or 5 half-lives (whichever is longer) prior to the Screening Period, or plans to use an investigational drug (other than the study drug) during the study.
10. Presence of renal impairment with a calculated creatinine clearance < 45 mL/min.
11. Laboratory value(s) outside the laboratory reference range that are considered to be clinically significant by the investigator (clinical chemistry). NOTE: clinical labs may be repeated once during the Screening Period
12. Participant has resistant hypertension, defined as one of the following: a. Controlled BP (ie, SBP < 140 mm Hg and DBP < 90 mm Hg) and treated with 4 or more antihypertensive medications. b. Uncontrolled BP (ie, SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg) despite concurrent use of 3 or more antihypertensive medications of different classes that include a diuretic.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to EOT Visit on the 24-hour average SBP (mm Hg)

Secondary endpoints 3

1. Change from baseline to EOT Visit on the daytime average SBP (mm Hg)
2. Change from baseline to EOT Visit on the seated resting average SBP (mm Hg)
3. Change from baseline to EOT Visit on the nighttime average SBP (mm Hg)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Jazz Pharmaceuticals PLC

Sponsor organisation

Jazz Pharmaceuticals PLC

Address

3170 Porter Drive

City

Palo Alto

Postcode

94304-1212

Country

United States

Scientific contact point

Organisation

Jazz Pharmaceuticals PLC

Contact name

Medical Monitor

Public contact point

Organisation

Jazz Pharmaceuticals PLC

Contact name

Medical Monitor

Third parties 4

Locations

5 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 168 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications