# Circadian rhythm disorders

[Home](../README.md) · [Sleep](../WATCHLIST.md#sleep-health) · [Calendar](../MILESTONES.md)

Tags: [Drugs and biologics](../BROWSE.md#drugs) · [Devices and procedures](../BROWSE.md#devices-procedures)

## Current state

Recovered September 29 sponsor data report a 37.1-minute earlier sleep onset versus placebo with tasimelteon in delayed-phase disorder. The small 28-day analysis lacks confidence intervals and detailed harms; registry results and any new indication remain pending.

Status: active. Topic ID: `sleep_circadian`.

## Questions to follow

- Follow delayed/advanced sleep-wake phase, non-24 and shift-work disorders as distinct conditions; retain sleep timing and work/light schedules.
- Compare timed light/dark exposure, behavioral scheduling and melatonin-based approaches using phase alignment, daily function and durable adherence.
- Keep circadian indications separate from general insomnia and jet-lag claims; verify elapsed regulatory proceedings without assuming an outcome.

## Programs and next milestones

### Focused update — 2026-10-16

<span class="note-anchor" id="note-2026-09-29-tasimelteon-dswpd-topline"></span>

#### Recovered tasimelteon topline reports earlier sleep timing in delayed-phase disorder

**September 29 sponsor release, recovered October 16 — NCT04652882.** Vanda reports that adults with delayed sleep-wake phase disorder receiving **tasimelteon 20 mg daily for 28 days** advanced diary-recorded sleep onset **42.5 minutes**, versus **5.4 minutes with placebo**: a **37.1-minute difference, p=.022**.

The release reports **43 enrolled**, but the numerical table covers **20 active and 20 placebo**; the remaining three and missing-data handling are unexplained. Confidence intervals are absent. An exploratory ≥30-minute response occurred in **12/20 versus 3/20** (p=.008).

The sponsor says no new safety signals, without adverse-event counts, discontinuations or detailed harms. Small size and short follow-up limit safety and durability. Earlier sleep timing is not proof of normalized circadian biomarkers, better sleep architecture or sustained daytime function.

This closes a saved search gap: the registry still has no posted results, but sponsor topline results do exist. Vanda plans an FDA discussion/supplemental application, with no verified filing or decision date. HETLIOZ’s existing U.S. Non-24/Smith-Magenis uses do **not** approve DSWPD.

**Sources:** [Source 1](https://www.prnewswire.com/news-releases/vanda-pharmaceuticals-announces-positive-phase-iii-results-for-hetlioztasimelteon-in-delayed-sleep-wake-phase-disorder-302893544.html); [Source 2](https://clinicaltrials.gov/study/NCT04652882).

**Remaining gaps:** Read current canonical scope, shared summaries, state and assigned topic notes. Bounded registry discovery covered July 18–October 16, 2026; prior October 13 findings were deduplicated. Full-topic successful-check dates remain unchanged.; Retrieved all 345 records across 4 pages of the bounded ClinicalTrials.gov query, plus 4 named records. Selected relevant new/changed protocols were appraised; downloading all records does not establish exhaustive safety/results review.; Europe PMC original-literature discovery failed with HTTP 503 for this topic. Targeted primary-source web searches supplied a partial fallback. Worldwide literature, regulators, international registries and complete original conference/podcast recordings remain incomplete.; The new condition baseline remains incomplete. Preceding 90-day registry discovery and selected inherited pivotal context were checked; the full older clinical, label and behavioral/device evidence corpus has not been completed.; Recovered September 29 tasimelteon sponsor topline closes a specific saved publication-access gap. Actual September completion and no registry results remain valid statements; saying no topline exists is no longer accurate. SUSTAIN and ICU studies refreshed without new results. Jet-lag hearing outcome, sustained phase/function evidence and full older baseline remain incomplete.

**Informal-source coverage:** Original Non-24/DSPD discussions include disability/access burden and personal timing responses, not new controlled efficacy or regulatory evidence. September tasimelteon topline was verified at the sponsor release rather than inferred from Reddit. Jet-lag hearing speculation remains unconfirmed; full audio incomplete.

[Full coverage record](../updates/2026-10-16_scheduled_research_update.md).


### Focused update — 2026-10-13

<span class="note-anchor" id="note-2026-10-09-tasimelteon-dswpd-completion-baseline"></span>

#### Delayed-phase tasimelteon trial now reports actual completion

**Status reconciliation, checked October 13 — NCT04652882.** Vanda's randomized masked Phase 3 tasimelteon-versus-placebo trial in delayed sleep-wake phase disorder now lists **completed, 43 actual participants**, with **September 4, 2026 actual primary/final completion**. The October 9 update was already retrievable at the prior run but not reconciled into the topic's elapsed-estimate description; this is a coverage correction, not newly released results.

Primary is diary-measured change in sleep-onset over **28 days**. No results are posted; completion does not prove improved circadian phase, daytime function or generalized insomnia benefit. Existing tasimelteon indications do not establish U.S. approval for DSWPD. A separate jet-lag hearing remains unresolved. Next: primary outcomes/harms and any sponsor readout; no date announced.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT04652882).

<span class="note-anchor" id="note-2026-10-13-icu-sleep-circadian"></span>

#### A new ICU protocol measures circadian hormones and sleep architecture

**NCT07869901, first posted October 13.** A recruiting nonrandomized unmasked **70-person** ICU study compares a multicomponent sleep/circadian package with usual care: reduced nighttime light/noise/care disruptions, daytime light/mobility and orientation.

Primary outcomes through day 3 are **recruitment, retention, data completeness and adherence**. Secondary measures include timed melatonin/cortisol, subjective sleep, actigraphy and **night 2 polysomnographic total sleep, N3 and REM percentages**. These are useful architecture/phase measures, but their improvement would not independently prove recovery, remission of a circadian disorder or better survival. Nonrandom allocation and the combined package limit causal/component interpretation.

Actual start **August 1, 2026**; estimated primary completion **June 30, 2027**, final **December 31, 2027**. No results or harms rates. This is hospital research, not a U.S. approved device/drug or an established at-home protocol.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07869901).

**Remaining gaps:** Read current canonical scope, shared summaries/state and assigned topic notes. September 5–October 13 overlap preserves the September 12 full-review dates; October 6/9 entries were deduplicated. All pages of each bounded ClinicalTrials.gov query were downloaded, and named records plus selected relevant new/changed protocols were appraised. This is focused partial review, not a worldwide full literature/regulator/safety census; successful full-topic dates must remain unchanged.; Bounded query retrieved 161 records across 2 pages; incidental studies excluded. Named topic records refreshed: 3. Full older evidence, international registries, comprehensive harms and all original conference/podcast recordings remain gaps.; New condition-specific baseline remains incomplete. Selected inherited older pivotal sources and newly recovered formal programs were reviewed, without declaring the preceding 90-day/older trial corpus complete.

**Informal-source coverage:** Targeted original DSPD, Non-24 and shift-work informal searches did not yield a distinct sourced development signal selected for inclusion. Some exact-date searches failed to return relevant posts. Full talks/audio, the jet-lag hearing outcome and disorder-specific patient-experience coverage remain incomplete.

[Full coverage record](../updates/2026-10-13_scheduled_research_update.md).


### Focused update — 2026-10-09

No additional finding was selected from the reviewed sources. Coverage remains incomplete; this is not a full-topic “no news” conclusion.

**Remaining gaps:** New condition baseline remains incomplete. Reviewed inherited hub, preceding 90-day development leads and selected older pivotal/contextual sources; October 6 findings deduplicated.; 93 named NCT records across the ten topics and ten discovery queries downloaded successfully through the ClinicalTrials.gov public API. Download is not a claim that all fields/safety/results were exhaustively appraised.; Focused review only. Do not advance full successful-check timestamps or label incomplete remaining searches as no news.; Circadian broad query returned 154 records; first 100 downloaded; selected relevant records screened, remainder incomplete, with many incidental/mechanistic and oncology timing matches. Timed light/dark and melatonin disorder-specific sustained phase/function baseline remains incomplete.; Tasimelteon jet-lag hearing outcome/date not verified. Searches still locate June 3 notice and elapsed July 20 prehearing plan; no conclusion inferred. Saved DSWPD and SUSTAIN registry milestones preserved as estimates; no new result found in those specific records.

**Informal-source coverage:** Original October 2 r/DSPD discussion and October4/5 comments reviewed through indexed text: individual timing/medicine/light experiences, no attributable new formal trial result or development leak. No broad efficacy conclusion from anecdotes; full podcast/talk appraisal remains incomplete.

[Full coverage record](../updates/2026-10-09_scheduled_research_update.md).


### Focused update — 2026-10-06

<span class="note-anchor" id="note-2026-07-27-tasimelteondswpd"></span>

#### Tasimelteon delayed-phase trial has an elapsed completion estimate

**Historical baseline addition reviewed October 6, 2026.** NCT04652882 is a randomized quadruple-masked placebo-controlled phase 3 tasimelteon study in delayed sleep-wake phase disorder, 70 planned adults. Primary endpoint: sleep-diary onset change over 28 days. ACTIVE_NOT_RECRUITING in the July 27 record; actual start December 9, 2020. September 2026 primary/final completion is still an estimate after that month elapsed, with no posted results. Existing Non-24/Smith-Magenis indications do not establish DSWPD, general insomnia or jet-lag approval. This is an older program newly added to the condition page; sustained phase alignment/daytime function and safety remain pending.

[Source 1](https://clinicaltrials.gov/api/v2/studies/NCT04652882) · [Source 2](https://clinicaltrials.gov/study/NCT04652882)

<span class="note-anchor" id="note-2026-07-24-sustain"></span>

#### SUSTAIN tests solriamfetol for shift-work sleepiness

**Historical baseline addition reviewed October 6, 2026.** SUSTAIN plans 520 adults with excessive sleepiness associated with shift-work disorder, randomized double-blind to two solriamfetol regimens or placebo for 12 weeks. Coprimary outcomes are MWT sleep latency and clinician-rated sleepiness severity during night shifts. RECRUITING in the July24 record, actual start August1,2024; primary/final completion is estimated December2026. No results posted. This measures alertness during shift work, not proven correction of circadian phase. Existing solriamfetol indications do not establish a shift-work approval. Safety, blood-pressure/heart-rate effects and longer-term real-work performance need result/label appraisal.

[Source 1](https://clinicaltrials.gov/api/v2/studies/NCT06568367) · [Source 2](https://clinicaltrials.gov/study/NCT06568367)

**Coverage:** 2026-10-06: circadian shift-work SeptemberOctober2026 clinicaltrials tasimelteon; 2026-10-06: tasimelteon July20 hearing2026 FDA docket query; 2026-10-06: circadian-condition interventional registry30latest; direct NCT04652882/NCT06568367; 2026-10-06: RedditDSPD/N24 SeptemberOctober2026; seasonal Hetlioz experience

**Remaining gaps:** Pending condition baseline partially expanded by DSWPD tasimelteon and SUSTAIN shift-work trials; latest30 circadian registry records screened with irrelevant mechanistic/consumer studies excluded.; Tasimelteon jet-lag prehearing July20 outcome/newdate not verified; FDA hearingnotice only. Timed light/dark/melatonin disorder-specific trials and pediatric/shiftwork broad baseline remain incomplete. SUSTAIN sponsor readout timing not freshly retrieved; registry completion is only an estimate.

**Informal-source coverage:** Sep11 r/N24 seasonal Hetlioz personal-experience lead surfaced, directpage fetch failed; no clinical development rumor promoted. No original circadian podcast/talk recording appraised.

[Full coverage record](../updates/2026-10-06_scheduled_research_update.md).


### Timed melatonin, light/dark exposure and sleep scheduling

**Development / U.S. status:** Intervention-specific human studies; the evidence below does not create a general drug approval or validate unsupervised timing protocols.

**Evidence / limitations:** A 2024 randomized active-strategy trial (NCT03715465) studied 40 adults with delayed sleep-wake phase disorder for four weeks. Both groups received low-dose melatonin, evening dim light and sleep scheduling. Measured-phase scheduling was not superior to estimated-phase scheduling; the package was not compared with placebo, and the study did not establish light-only efficacy.

**Next milestone:** Larger comparisons, sustained phase alignment and daytime function; no reliable readout date verified. [Primary study](https://pmc.ncbi.nlm.nih.gov/articles/PMC11217625/) · [Registry](https://clinicaltrials.gov/study/NCT03715465) · [Original detailed notes](12_sleep.md#sleep-circadian-baseline).

### Tasimelteon / Hetlioz

**Development / U.S. status:** Indication-specific U.S. uses include adult Non-24-Hour Sleep-Wake Disorder and defined Smith-Magenis sleep-disturbance populations; not a general insomnia or jet-lag approval.

**Evidence / limitations:** The June 3, 2026 FDA hearing notice concerned proposed refusal of a jet-lag supplemental application and scheduled a July 20 prehearing conference. Earlier checks did not verify the completed hearing or a decision; an elapsed procedural date is not a clinical or regulatory outcome.

**Next milestone:** Verify the docket/hearing outcome; no firm new date established. [FDA label](https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/205677Orig1s013lbl.pdf) · [Official hearing notice](https://www.govinfo.gov/content/pkg/FR-2026-06-03/pdf/2026-11046.pdf).

## Dated history

### October 3, 2026 — Topic organization

Created this condition-specific entry from existing sleep coverage. Earlier sources, program dates, historical findings and successful research-check timestamps were preserved. See the [organization record](../updates/2026-10-03_sleep_category_organization.md) and [original history](12_sleep.md#dated-history). This is a navigation and baseline projection, not a new medical-news event.